The Chinese tree shrew has gained prominence as a model organism due to its phylogenetic proximity to primates,offering distinct advantages over traditional rodent models in biomedical research.However,the neuroanatom...The Chinese tree shrew has gained prominence as a model organism due to its phylogenetic proximity to primates,offering distinct advantages over traditional rodent models in biomedical research.However,the neuroanatomy of this species remains insufficiently defined,limiting its utility in neurophysiological and neuropathological studies.In this study,immunofluorescence microscopy was employed to comprehensively map the distribution of three calciumbinding proteins,parvalbumin,calbindin D-28k,and calretinin,across the tree shrew cerebrum.Serial brain sections in sagittal,coronal,and horizontal planes from 12 individuals generated a dataset of 3638 cellular-resolution images.This dataset,accessible via Science Data Bank(https://doi.org/10.57760/sciencedb.23471),provides detailed region-and laminar-selective distributions of calcium-binding proteins valuable for the cyto-and chemoarchitectural characterization of the tree shrew cerebrum.This resource will not only advance our understanding of brain organization and facilitate basic and translational neuroscience research in tree shrews but also enhance comparative and evolutionary analyses across species.展开更多
Astrocytes are associated with varying brain size between rodents and primates.As a close evolutionary relative of primates,the tree shrew(Tupaia belangeri)provides a valuable comparative model for investigating glial...Astrocytes are associated with varying brain size between rodents and primates.As a close evolutionary relative of primates,the tree shrew(Tupaia belangeri)provides a valuable comparative model for investigating glial architecture.However,the anatomical distribution and morphological characteristics of astrocytes in the tree shrew brain remain poorly characterized.In this study,glial fibrillary acidic protein(GFAP)immunofluorescence was employed to systematically examine the spatial distribution and morphology of astrocytes in the whole brain of tree shrews.Notably,GFAP-immunoreactive(ir)astrocytes were detected throughout the telencephalon,diencephalon,mesencephalon,metencephalon,and myelencephalon.Distinct laminar distribution was evident in regions such as the main olfactory bulb and hippocampus.Semi-quantitative comparisons revealed significant regional differences in astrocyte density between tree shrews and mice,encompassing the main olfactory bulb,accessory olfactory bulb,olfactory tubercle,cortex,hippocampus,cortical amygdaloid nucleus,hypothalamus,thalamus,superior colliculus,interpeduncular nucleus,median raphe nucleus,and parabrachial nucleus.Compared to mice,tree shrews exhibited higher astrocyte density with increased morphological complexity in the posterior hypothalamic nucleus,dorsomedial hypothalamic nucleus,ventromedial hypothalamic nucleus,and periaqueductal gray,but lower density with greater morphological complexity in the hippocampus and substantia nigra.In the paraventricular hypothalamic nucleus and lateral hypothalamic area,GFAP-ir astrocytes displayed comparable densities between tree shrews and mice but exhibited region-specific differences in morphological complexity.This study provides the first brain-wide mapping of GFAP-ir astrocytes in tree shrews,revealing marked interspecies differences in their distribution and morphology,and establishing a neuroanatomical framework for understanding astrocyte involvement in diverse physiological and behavioral functions.展开更多
Background:Q uantifying the rich home-c age activities of tree shrews provides a reliable basis for understanding their daily routines and building disease models.However,due to the lack of effective behavioral method...Background:Q uantifying the rich home-c age activities of tree shrews provides a reliable basis for understanding their daily routines and building disease models.However,due to the lack of effective behavioral methods,most efforts on tree shrew behavior are limited to simple measures,resulting in the loss of much behavioral information.Methods:T o address this issue,we present a deep learning(DL)approach to achieve markerless pose estimation and recognize multiple spontaneous behaviors of tree shrews,including drinking,eating,resting,and staying in the dark house,etc.Results:T his high-t hroughput approach can monitor the home-cage activities of 16 tree shrews simultaneously over an extended period.Additionally,we demonstrated an innovative system with reliable apparatus,paradigms,and analysis methods for investigating food grasping behavior.The median duration for each bout of grasping was 0.20 s.Conclusion:T his study provides an efficient tool for quantifying and understand tree shrews'natural behaviors.展开更多
The family Hepeviridae has seen an explosive expansion in its host range in recent years,yet the evolutionary trajectory of this zoonotic pathogen remains largely unknown.The emergence of rat hepatitis E virus(HEV)has...The family Hepeviridae has seen an explosive expansion in its host range in recent years,yet the evolutionary trajectory of this zoonotic pathogen remains largely unknown.The emergence of rat hepatitis E virus(HEV)has introduced a new public health threat due to its potential for zoonotic transmission.This study investigated2?464 wild small mammals spanning four animal orders,eight families,21 genera,and 37 species in Yunnan Province,China.Using broadly reactive reverse transcription-polymerase chain reaction(RT-PCR),we systematically screened the presence and prevalence of Orthohepevirus and identified 192 positive specimens from10 species,corresponding to an overall detection rate of7.79%.Next-generation sequencing enabled the recovery of 24 full-length genomic sequences from eight host species,including Bandicota bengalensis,Eothenomys eleusis,and Episoriculus caudatus,representing newly reported host species for Orthohepevirus strains.Phylogenetic and sequence analyses revealed extensive genetic diversity within orthohepeviruses infecting rodents and shrews.Notably,among the identified strains,20 were classified as Rocahepevirus ratti C1,two as C3,and one as Rocahepevirus eothenomi,while the remaining strain exhibited significant divergence,precluding classification.Evolutionary analyses highlighted close associations between orthohepeviruses and their respective host taxa,with distinct phylogenetic clustering patterns observed across different host orders.These findings emphasize the critical roles of co-speciation and cross-species transmission in shaping the evolutionary trajectories of the genera Paslahepevirus and Rocahepevirus.展开更多
Viruses circulating in small mammals possess the potential to infect humans.Tree shrews are a group of small mammals inhabiting widely in forests and plantations,but studies on viruses in tree shrews are quite limited...Viruses circulating in small mammals possess the potential to infect humans.Tree shrews are a group of small mammals inhabiting widely in forests and plantations,but studies on viruses in tree shrews are quite limited.Herein,viral metagenomic sequencing was employed to detect the virome in the tissue and swab samples from seventy-six tree shrews that we collected in Yunnan Province.As the results,genomic fragments belonging to eighteen viral families were identified,thirteen of which contain mammalian viruses.Through polymerase chain reaction(PCR)and Sanger sequencing,twelve complete genomes were determined,including five parvoviruses,three torque teno viruses(TTVs),two adenoviruses,one pneumovirus,and one hepacivirus,together with three partial genomes,including two hepatitis E viruses and one paramyxovirus.Notably,the three TTVs,named TSTTV-HNU1,TSTTV-HNU2,and TSTTV-HNU3,may compose a new genus within the family Anelloviridae.Notably,TSParvoV-HNU5,one of the tree shrew parvoviruses detected,was likely to be a recombination of two murine viruses.Divergence time estimation further revealed the potential cross-species-transmission history of the tree shrew pneumovirus TSPneV-HNU1.Our study provides a comprehensive exploration of viral diversity in wild tree shrews,significantly enhancing our understanding of their roles as natural virus reservoirs.展开更多
Following the publication of Zeng et al.(2023),an inadvertent error was recently identified in Figure 1B and Supplementary Figure S3.To ensure the accuracy and integrity of our published work,we formally request a cor...Following the publication of Zeng et al.(2023),an inadvertent error was recently identified in Figure 1B and Supplementary Figure S3.To ensure the accuracy and integrity of our published work,we formally request a correction to address this issue and apologize for any confusion this error may have caused.For details,please refer to the modified Supplementary Materials.展开更多
The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent year...The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.展开更多
The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their produc...The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.展开更多
The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.Th...The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.展开更多
Recent genome studies indicate that tree shrew is in the order or a closest sister of primates,and thus may be one of the best animals to model human diseases.In this paper,we report on a social defeat model of depres...Recent genome studies indicate that tree shrew is in the order or a closest sister of primates,and thus may be one of the best animals to model human diseases.In this paper,we report on a social defeat model of depression in tree shrew（Tupaia belangeri chinensis）.Two male tree shrews were housed in a pair-cage consisting of two independent cages separated by a wire mesh partition with a door connecting the two cages.After one week adaptation,the connecting door was opened and a brief fighting occurs between the two male tree shrews and this social conflict session consisted of 1 h direct conflict（fighting） and 23 h indirect influence（e.g.smell,visual cues） per day for 21 days.The defeated tree shrew was considered the subordinate.Compared with na？ve animals,subordinate tree shrews at the final week of social conflict session showed alterations in body weight,locomotion,avoidance behavior and urinary cortisol levels.Remarkably,these alterations persisted for over two weeks.We also report on a novel captive conditioning model of learning and memory in tree shrew.An automatic trapping cage was placed in a small closed room with a freely-moving tree shrew.For the first four trials,the tree shrew was not trapped when it entered the cage and ate the bait apple,but it was trapped and kept in the cage for 1 h on the fifth trial.Latency was defined as the time between release of the tree shrew and when it entered the captive cage.Latencies during the five trials indicated adaptation.A test trial 24 h later was used to measure whether the one-trial trapping during the fifth trial could form captive memory.Tree shrews showed much longer trapping latencies in the test trial than the adaptation trials.The N-methyl-d-aspartate（NMDA） receptor antagonist MK-801（0.2 mg/kg,i.p.）,known to prevent the formation of memory,did not affect latencies in the adaptation trails,but did block captive memory as it led to much shorter trapping latencies compared to saline treatment in the test trial.These results demonstrate a chronic social defeat model of depression and a novel one-trial captive conditioning model for learning and memory in tree shrews,which are important for mechanism studies of depression,learning,memory,and preclinical evaluation for new antidepressants.展开更多
Breast cancer is a common malignant tumor.It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches.Tree shrews（Tupaia belangeri chinensis） have a closer evolution...Breast cancer is a common malignant tumor.It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches.Tree shrews（Tupaia belangeri chinensis） have a closer evolutionary relationship with humans than do rodents,which have been widely used in laboratory research.Spontaneous breast tumors were identified in tree shrews in 1960s;however,no detailed studies about tree shrew breast tumors have been conducted to date.Here,we characterized a spontaneous breast tumor from tree shrews by Haematoxylin Eosin（HE） staining.This tumor was identified as a papillary tumor.Immunohistochemical staining（IHC） for progesterone receptor（PR）,Ki-67 and cleaved caspase-3 showed that tumor cells were positive for PR,highly proliferative,and less apoptotic compared to normal breast epithelial cells.Thus,the spontaneous tumor of tree shrew is very close to human papillary tumors in terms of morphology and pathology and we concluded that tree shrew may be a suitable animal model for breast cancer research.展开更多
Due to their special phylogenetic position in the Euarchontoglires and close affinity to primates,tree shrews have been proposed as an alternative experimental animal to primates in biomedical research.However,the pop...Due to their special phylogenetic position in the Euarchontoglires and close affinity to primates,tree shrews have been proposed as an alternative experimental animal to primates in biomedical research.However,the population genetic structure of tree shrews has largely remained unknown and this has hindered the development of tree shrew breeding and selection.Here we sampled 80 Chinese tree shrews（Tupaia belangeri chinensis） in Kunming,China,and analyzed partial mtDNA control region sequence variation.Based on our samples and two published sequences from northern tree shrews（T.belangeri）,we identified 29 substitutions in the mtDNA control region fragment（～ 604 bp） across 82 individuals and defined 13 haplotypes.Seventeen samples were selected for sequencing of the cytochrome b（Cyt b;1134 bp） gene based on control region sequence variation and were analyzed in combination with 34 published sequences to solidify the phylogenetic pattern obtained from control region data.Overall,tree shrews from Kunming have high genetic diversity and present a remarkable long genetic distance to the two reported northern tree shrews outside China.Our results provide some caution when using tree shrews to establish animal models because of this apparent genetic difference.In addition,the high genetic diversity of Chinese tree shrews inhabiting Kunming suggests that systematic genetic investigations should be conducted before establishing an inbred strain for medical and biological research.展开更多
Animal models are essential for the development of new anti-infectious drugs.Although some bacterial infection models have been established in rodents,small primate models are rare.Here,we report on two bacterial infe...Animal models are essential for the development of new anti-infectious drugs.Although some bacterial infection models have been established in rodents,small primate models are rare.Here,we report on two bacterial infection models established in tree shrew（Tupaia belangeri chinensis）.A burnt skin infection model was induced by dropping 5×106 CFU of Staphylococcus aureus on the surface of a wound after a third degree burn.This dose of S.aureus caused persistent infection for 7 days and obvious inflammatory response was observed 4 days after inoculation.A Dacron graft infection model,2×106 CFU of Pseudomonas aeruginosa also caused persistent infection for 6 days,with large amounts of pus observed 3 days after inoculation.These models were used to evaluate the efficacy of levofloxacin（LEV） and cefoperazone（CPZ）,which reduced the viable bacteria in skin to 4log10 and 5log10 CFU/100 mg tissue,respectively.The number of bacteria in graft was significantly reduced by 4log10 CFU/mL treatment compared to the untreated group（P0.05）.These results suggest that two bacterial infection models were successfully established in tree shrew using P.aeruginosa and S.aureus.In addition,tree shrew was susceptible to P.aeruginosa and S.aureus,thus making it an ideal bacterial infection animal model for the evaluation of new antimicrobials.展开更多
鉴于原猿类的树鼩在进化中的特殊地位,有关它的神经生物学研究十分活跃。树鼩的单位放电研究已有报告(J. E. Abano et al. 1978;A. L. Humphrey et al. 1977、1980),但是采用慢性微电极技术记录行为状态的树鼩的单位放电方法迄今未见报...鉴于原猿类的树鼩在进化中的特殊地位,有关它的神经生物学研究十分活跃。树鼩的单位放电研究已有报告(J. E. Abano et al. 1978;A. L. Humphrey et al. 1977、1980),但是采用慢性微电极技术记录行为状态的树鼩的单位放电方法迄今未见报道,本文报告一种记录清醒活动状态树鼩的单位放电技术考虑到树鼩形体甚小、体重仅100多克。要分离单位放电,必须拥有一种特殊规格的微型微推进器,以适应特殊实验之需。本研究设计一种采用差动结构原理实现微推进的装置,整个装置由微推进器与基座组成。微推进器的参数如下:重量8.8克;微调范围:2.0毫米;微调读数5微米;微调可控范围:小于2微米;外形尺寸:13×13×51毫米。微推进器相对于基座有直径为1.8毫米的径向偏心移动范围。基座重0.65克,实验在局麻下,在立体定向仪控制下埋植基座。术后第二天即可实验观察。展开更多
The Chinese tree shrew （Tupaia belangeri chinensis） a squirrel-like and rat-sized mammal, has a wide distribution in Southeast Asia, South and Southwest China and has many unique characteristics that make it suitabl...The Chinese tree shrew （Tupaia belangeri chinensis） a squirrel-like and rat-sized mammal, has a wide distribution in Southeast Asia, South and Southwest China and has many unique characteristics that make it suitable for use as an experimental animal. There have been many studies using the tree shrew （Tupaia belangeri） aimed at increasing our understanding of fundamental biological mechanisms and for the modeling of human diseases and therapeutic responses. The recent release of a publicly available annotated genome sequence of the Chinese tree shrew and its genome database （www.treeshrewdb.org） has offered a solid base from which it is possible to elucidate the basic biological properties and create animal models using this species. The extensive characterization of key factors and signaling pathways in the immune and nervous systems has shown that tree shrews possess both conserved and unique features relative to primates. Hitherto, the tree shrew has been successfully used to create animal models for myopia, depression, breast cancer, alcohol-induced or non-alcoholic fatty liver diseases, herpes simplex virus type 1 （HSV-1） and hepatitis C virus （HCV） infections, to name a few. The recent successful genetic manipulation of the tree shrew has opened a new avenue for the wider usage of this animal in biomedical research. In this opinion paper, I attempt to summarize the recent research advances that have used the Chinese tree shrew, with a focus on the new knowledge obtained by using the biological properties identified using the tree shrew genome, a proposal for the genome-based approach for creating animal models, and the genetic manipulation of the tree shrew. With more studies using this species and the application of cutting-edge gene editing techniques, the tree shrew will continue to be under the spot light as a viable animal model for investigating the basis of many different human diseases.展开更多
The tree shrew （Tupaia belangeri） is a promising laboratory animal that possesses a closer genetic relationship to primates than to rodents. In addition, advantages such as small size, easy breeding, and rapid repro...The tree shrew （Tupaia belangeri） is a promising laboratory animal that possesses a closer genetic relationship to primates than to rodents. In addition, advantages such as small size, easy breeding, and rapid reproduction make the tree shrew an ideal subject for the study of human disease. Numerous tree shrew disease models have been generated in biological and medical studies in recent years. Here we summarize current tree shrew disease models, including models of infectious diseases, cancers, depressive disorders, drug addiction, myopia, metabolic diseases, and immune-related diseases. With the success of tree shrew transgenic technology, this species will be increasingly used in biological and medical studies in the future.展开更多
Tree shrew （Tupaia belangeri） is currently placed in Order Scandentia and has a wide distribution in Southeast Asia and Southwest China. Due to its unique characteristics, such as small body size, high brain-to-body...Tree shrew （Tupaia belangeri） is currently placed in Order Scandentia and has a wide distribution in Southeast Asia and Southwest China. Due to its unique characteristics, such as small body size, high brain-to-body mass ratio, short reproductive cycle and life span, and low-cost of maintenance, tree shrew has been proposed to be an alternative experimental animal to primates in biomedical research. However, there are some debates regarding the exact phylogenetic affinity of tree shrew to primates. In this study, we determined the mtDNA entire genomes of three Chinese tree shrews （T. belangeri chinensis） and one Malayan flying lemur （Galeopterus variegatus）. Combined with the published data for species in Euarchonta, we intended to diseen] the phylogenetic relationship among representative species of Dermoptera, Scandentia and Primates. The mtDNA genomes of Chinese tree shrews and Malayan flying lemur shared similar gene organization and structure with those of other mammals. Phylogenetic analysis based on 12 concatenated mitochondrial proteinencoding genes revealed a closer relationship between species of Scandentia and Glires, whereas species of Dermoptera were clustered with Primates. This pattern was consistent with previously reported phylogeny based on mtDNA data, but differed from the one reconstructed on the basis of nuclear genes. Our result suggested that the matrilineal affinity of tree shrew to primates may not be as close as we had thought. The ongoing project for sequencing the entire genome of Chinese tree shrew will provide more information to clarify this important issue.展开更多
The Chinese tree shrew(Tupaia belangeri chinensis)is emerging as an important experimental animal in multiple fields of biomedical research.Comprehensive reference genome annotation for both mRNA and long non-coding R...The Chinese tree shrew(Tupaia belangeri chinensis)is emerging as an important experimental animal in multiple fields of biomedical research.Comprehensive reference genome annotation for both mRNA and long non-coding RNA(lncRNA)is crucial for developing animal models using this species.In the current study,we collected a total of 234 high-quality RNA sequencing(RNA-seq)datasets and two long-read isoform sequencing(ISO-seq)datasets and improved the annotation of our previously assembled high-quality chromosomelevel tree shrew genome.We obtained a total of 3514 newly annotated coding genes and 50576 lncRNA genes.We also characterized the tissuespecific expression patterns and alternative splicing patterns of mRNAs and lncRNAs and mapped the orthologous relationships among 11 mammalian species using the current annotated genome.We identified 144 tree shrew-specific gene families,including interleukin 6(IL6)and STT3 oligosaccharyltransferase complex catalytic subunit B(STT3B),which underwent significant changes in size.Comparison of the overall expression patterns in tissues and pathways across four species(human,rhesus monkey,tree shrew,and mouse)indicated that tree shrews are more similar to primates than to mice at the tissue-transcriptome level.Notably,the newly annotated purine rich element binding protein A(PURA)gene and the STT3B gene family showed dysregulation upon viral infection.The updated version of the tree shrew genome annotation(KIZ version 3:TS_3.0)is available at http://www.treeshrewdb.org and provides an essential reference for basic and biomedical studies using tree shrew animal models.展开更多
Coxsackie virus A16(CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease(HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and ...Coxsackie virus A16(CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease(HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and severe inflammatory CNS lesions. In this study, experimentally CA16 infected tree shrews(Tupaia belangeri) were used to investigate CA16 pathogenesis. The results showed that both the body temperature and the percentages of blood neutrophilic granulocytes / monocytes of CA16 infected tree shrews increased at 4-7 days post infection. Dynamic distributions of CA16 in different tissues and stools were found at different infection stages. Moreover, the pathological changes in CNS and other organs were also observed. These findings indicate that tree shrews can be used as a viable animal model to study CA16 infection.展开更多
基金supported by the Science and Technology Innovation(STI)2030-Major Projects(2022ZD0205000 to L.L.)CAS“Light of West China”Program(xbzg-zdsys-202404 to L.L.)+1 种基金Yunnan Revitalization Talent Support Program Yunling Scholar Project(to L.L.)Yunnan Fundamental Research Projects(202305AH340006,202301AS070060 to L.L.,202401AT070206 to X.C.)。
文摘The Chinese tree shrew has gained prominence as a model organism due to its phylogenetic proximity to primates,offering distinct advantages over traditional rodent models in biomedical research.However,the neuroanatomy of this species remains insufficiently defined,limiting its utility in neurophysiological and neuropathological studies.In this study,immunofluorescence microscopy was employed to comprehensively map the distribution of three calciumbinding proteins,parvalbumin,calbindin D-28k,and calretinin,across the tree shrew cerebrum.Serial brain sections in sagittal,coronal,and horizontal planes from 12 individuals generated a dataset of 3638 cellular-resolution images.This dataset,accessible via Science Data Bank(https://doi.org/10.57760/sciencedb.23471),provides detailed region-and laminar-selective distributions of calcium-binding proteins valuable for the cyto-and chemoarchitectural characterization of the tree shrew cerebrum.This resource will not only advance our understanding of brain organization and facilitate basic and translational neuroscience research in tree shrews but also enhance comparative and evolutionary analyses across species.
基金supported by the STI2030-Major Projects(2022ZD0205202)Anhui Provincial Natural Science Foundation(2408085Y043)National Natural Science Foundation of China(82471540,32030046,32200798)。
文摘Astrocytes are associated with varying brain size between rodents and primates.As a close evolutionary relative of primates,the tree shrew(Tupaia belangeri)provides a valuable comparative model for investigating glial architecture.However,the anatomical distribution and morphological characteristics of astrocytes in the tree shrew brain remain poorly characterized.In this study,glial fibrillary acidic protein(GFAP)immunofluorescence was employed to systematically examine the spatial distribution and morphology of astrocytes in the whole brain of tree shrews.Notably,GFAP-immunoreactive(ir)astrocytes were detected throughout the telencephalon,diencephalon,mesencephalon,metencephalon,and myelencephalon.Distinct laminar distribution was evident in regions such as the main olfactory bulb and hippocampus.Semi-quantitative comparisons revealed significant regional differences in astrocyte density between tree shrews and mice,encompassing the main olfactory bulb,accessory olfactory bulb,olfactory tubercle,cortex,hippocampus,cortical amygdaloid nucleus,hypothalamus,thalamus,superior colliculus,interpeduncular nucleus,median raphe nucleus,and parabrachial nucleus.Compared to mice,tree shrews exhibited higher astrocyte density with increased morphological complexity in the posterior hypothalamic nucleus,dorsomedial hypothalamic nucleus,ventromedial hypothalamic nucleus,and periaqueductal gray,but lower density with greater morphological complexity in the hippocampus and substantia nigra.In the paraventricular hypothalamic nucleus and lateral hypothalamic area,GFAP-ir astrocytes displayed comparable densities between tree shrews and mice but exhibited region-specific differences in morphological complexity.This study provides the first brain-wide mapping of GFAP-ir astrocytes in tree shrews,revealing marked interspecies differences in their distribution and morphology,and establishing a neuroanatomical framework for understanding astrocyte involvement in diverse physiological and behavioral functions.
基金supported by grants from the National Key Research and Development Program of China(2023YFF0724902)the China Postdoctoral Science Foundation(2020?M670027,2023TQ0183)the Local Standards Research of BeiJing Laboratory Tree Shrew(CHYX-2023-DGB001)。
文摘Background:Q uantifying the rich home-c age activities of tree shrews provides a reliable basis for understanding their daily routines and building disease models.However,due to the lack of effective behavioral methods,most efforts on tree shrew behavior are limited to simple measures,resulting in the loss of much behavioral information.Methods:T o address this issue,we present a deep learning(DL)approach to achieve markerless pose estimation and recognize multiple spontaneous behaviors of tree shrews,including drinking,eating,resting,and staying in the dark house,etc.Results:T his high-t hroughput approach can monitor the home-cage activities of 16 tree shrews simultaneously over an extended period.Additionally,we demonstrated an innovative system with reliable apparatus,paradigms,and analysis methods for investigating food grasping behavior.The median duration for each bout of grasping was 0.20 s.Conclusion:T his study provides an efficient tool for quantifying and understand tree shrews'natural behaviors.
基金supported by the National Natural Science Foundation of China (U2002218,81874274)Yunnan Health Training Project of High Level Talents (L-2017027)+3 种基金Project of Cross-border Control and Quarantine Innovation Group of Zoonosis of Dali University (ZKPY2019302)to Y.Z.ZOpen Project of Yunnan Key Laboratory of Biodiversity Information (BIKF22-02)Youth Innovation Promotion Association of the Chinese Academy of SciencesYunnan Revitalization Talent Support Program Young Talent Project to X.L.Y。
文摘The family Hepeviridae has seen an explosive expansion in its host range in recent years,yet the evolutionary trajectory of this zoonotic pathogen remains largely unknown.The emergence of rat hepatitis E virus(HEV)has introduced a new public health threat due to its potential for zoonotic transmission.This study investigated2?464 wild small mammals spanning four animal orders,eight families,21 genera,and 37 species in Yunnan Province,China.Using broadly reactive reverse transcription-polymerase chain reaction(RT-PCR),we systematically screened the presence and prevalence of Orthohepevirus and identified 192 positive specimens from10 species,corresponding to an overall detection rate of7.79%.Next-generation sequencing enabled the recovery of 24 full-length genomic sequences from eight host species,including Bandicota bengalensis,Eothenomys eleusis,and Episoriculus caudatus,representing newly reported host species for Orthohepevirus strains.Phylogenetic and sequence analyses revealed extensive genetic diversity within orthohepeviruses infecting rodents and shrews.Notably,among the identified strains,20 were classified as Rocahepevirus ratti C1,two as C3,and one as Rocahepevirus eothenomi,while the remaining strain exhibited significant divergence,precluding classification.Evolutionary analyses highlighted close associations between orthohepeviruses and their respective host taxa,with distinct phylogenetic clustering patterns observed across different host orders.These findings emphasize the critical roles of co-speciation and cross-species transmission in shaping the evolutionary trajectories of the genera Paslahepevirus and Rocahepevirus.
基金funded by the National Natural Science Foundation of China(No.U2002218)the Science and Technology Innovation Program of Hunan Province(2024RC1028)Hunan University(No.521119400156).
文摘Viruses circulating in small mammals possess the potential to infect humans.Tree shrews are a group of small mammals inhabiting widely in forests and plantations,but studies on viruses in tree shrews are quite limited.Herein,viral metagenomic sequencing was employed to detect the virome in the tissue and swab samples from seventy-six tree shrews that we collected in Yunnan Province.As the results,genomic fragments belonging to eighteen viral families were identified,thirteen of which contain mammalian viruses.Through polymerase chain reaction(PCR)and Sanger sequencing,twelve complete genomes were determined,including five parvoviruses,three torque teno viruses(TTVs),two adenoviruses,one pneumovirus,and one hepacivirus,together with three partial genomes,including two hepatitis E viruses and one paramyxovirus.Notably,the three TTVs,named TSTTV-HNU1,TSTTV-HNU2,and TSTTV-HNU3,may compose a new genus within the family Anelloviridae.Notably,TSParvoV-HNU5,one of the tree shrew parvoviruses detected,was likely to be a recombination of two murine viruses.Divergence time estimation further revealed the potential cross-species-transmission history of the tree shrew pneumovirus TSPneV-HNU1.Our study provides a comprehensive exploration of viral diversity in wild tree shrews,significantly enhancing our understanding of their roles as natural virus reservoirs.
文摘Following the publication of Zeng et al.(2023),an inadvertent error was recently identified in Figure 1B and Supplementary Figure S3.To ensure the accuracy and integrity of our published work,we formally request a correction to address this issue and apologize for any confusion this error may have caused.For details,please refer to the modified Supplementary Materials.
基金supported by the STI2030-Major Projects(2021ZD0200900 to Y.G.Y.)"Light of West China" Program of the Chinese Academy of Sciences(xbzg-zdsys-202302 to Y.G.Y.)
文摘The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.
基金supported by the Key Research and Development Program of Guangxi(2021AB13014)Major Project of Guangxi Innovation Driven(AA18118016)+7 种基金National Key Research and Development Program of China(2017YFC0908000)Natural Key Research and Development Project(2020YFA0113200)National Natural Science Foundation of China(81770759,82060145,31970814)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2021JJA140912)Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University,Guangxi Key Laboratory for Genomic and Personalized Medicine(19-050-22,19-185-33,20-065-33,22-35-17)Major Project of Scientific Research and Technology Development Plan of Nanning(20221023)Guangxi Natural Science Foundation(2022GXNSFAA035641)Self-funded Project of Health Commission of Guangxi Zhuang Autonomous Region(Z-A20230620)。
文摘The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.
基金supported by the National Key R&D Program of China (2021YFC2300900,2021YFC2301300)Academic Promotion Programme of Shandong First Medical University (2019QL006)+2 种基金Natural Science Foundation of Shandong Province (ZR2020QH274)Yunnan Key Research and Development Program (202103AQ100001,202102AA310055)Key Program of Chinese Academy of Sciences (KJZD-SW-L11)。
文摘The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.
基金supported by grants KSCX2-EW-R-12 and KSCX2-EW-J-23 from the Chinese Academy of Sciences
文摘Recent genome studies indicate that tree shrew is in the order or a closest sister of primates,and thus may be one of the best animals to model human diseases.In this paper,we report on a social defeat model of depression in tree shrew（Tupaia belangeri chinensis）.Two male tree shrews were housed in a pair-cage consisting of two independent cages separated by a wire mesh partition with a door connecting the two cages.After one week adaptation,the connecting door was opened and a brief fighting occurs between the two male tree shrews and this social conflict session consisted of 1 h direct conflict（fighting） and 23 h indirect influence（e.g.smell,visual cues） per day for 21 days.The defeated tree shrew was considered the subordinate.Compared with na？ve animals,subordinate tree shrews at the final week of social conflict session showed alterations in body weight,locomotion,avoidance behavior and urinary cortisol levels.Remarkably,these alterations persisted for over two weeks.We also report on a novel captive conditioning model of learning and memory in tree shrew.An automatic trapping cage was placed in a small closed room with a freely-moving tree shrew.For the first four trials,the tree shrew was not trapped when it entered the cage and ate the bait apple,but it was trapped and kept in the cage for 1 h on the fifth trial.Latency was defined as the time between release of the tree shrew and when it entered the captive cage.Latencies during the five trials indicated adaptation.A test trial 24 h later was used to measure whether the one-trial trapping during the fifth trial could form captive memory.Tree shrews showed much longer trapping latencies in the test trial than the adaptation trials.The N-methyl-d-aspartate（NMDA） receptor antagonist MK-801（0.2 mg/kg,i.p.）,known to prevent the formation of memory,did not affect latencies in the adaptation trails,but did block captive memory as it led to much shorter trapping latencies compared to saline treatment in the test trial.These results demonstrate a chronic social defeat model of depression and a novel one-trial captive conditioning model for learning and memory in tree shrews,which are important for mechanism studies of depression,learning,memory,and preclinical evaluation for new antidepressants.
基金Yunnan Province High-Profile Talent Project (2010CI114)the Chinese Academy of Sciences,Basic Frontier Project (KSCX2-EW-J-23)
文摘Breast cancer is a common malignant tumor.It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches.Tree shrews（Tupaia belangeri chinensis） have a closer evolutionary relationship with humans than do rodents,which have been widely used in laboratory research.Spontaneous breast tumors were identified in tree shrews in 1960s;however,no detailed studies about tree shrew breast tumors have been conducted to date.Here,we characterized a spontaneous breast tumor from tree shrews by Haematoxylin Eosin（HE） staining.This tumor was identified as a papillary tumor.Immunohistochemical staining（IHC） for progesterone receptor（PR）,Ki-67 and cleaved caspase-3 showed that tumor cells were positive for PR,highly proliferative,and less apoptotic compared to normal breast epithelial cells.Thus,the spontaneous tumor of tree shrew is very close to human papillary tumors in terms of morphology and pathology and we concluded that tree shrew may be a suitable animal model for breast cancer research.
基金supported by grants from Yunnan Province (2009CI119)the Chinese Academy of Sciences (KSCX2-EW-R-11 and KSCX2-EW-J-23)the Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province
文摘Due to their special phylogenetic position in the Euarchontoglires and close affinity to primates,tree shrews have been proposed as an alternative experimental animal to primates in biomedical research.However,the population genetic structure of tree shrews has largely remained unknown and this has hindered the development of tree shrew breeding and selection.Here we sampled 80 Chinese tree shrews（Tupaia belangeri chinensis） in Kunming,China,and analyzed partial mtDNA control region sequence variation.Based on our samples and two published sequences from northern tree shrews（T.belangeri）,we identified 29 substitutions in the mtDNA control region fragment（～ 604 bp） across 82 individuals and defined 13 haplotypes.Seventeen samples were selected for sequencing of the cytochrome b（Cyt b;1134 bp） gene based on control region sequence variation and were analyzed in combination with 34 published sequences to solidify the phylogenetic pattern obtained from control region data.Overall,tree shrews from Kunming have high genetic diversity and present a remarkable long genetic distance to the two reported northern tree shrews outside China.Our results provide some caution when using tree shrews to establish animal models because of this apparent genetic difference.In addition,the high genetic diversity of Chinese tree shrews inhabiting Kunming suggests that systematic genetic investigations should be conducted before establishing an inbred strain for medical and biological research.
基金financially supported by the Project from the Chinese Academy of Sciences (KSCX2-EW-R-11)the Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province (KSCX2-EW-J-23)Science and Technology Department of Yunnan Province (2011C1139)
文摘Animal models are essential for the development of new anti-infectious drugs.Although some bacterial infection models have been established in rodents,small primate models are rare.Here,we report on two bacterial infection models established in tree shrew（Tupaia belangeri chinensis）.A burnt skin infection model was induced by dropping 5×106 CFU of Staphylococcus aureus on the surface of a wound after a third degree burn.This dose of S.aureus caused persistent infection for 7 days and obvious inflammatory response was observed 4 days after inoculation.A Dacron graft infection model,2×106 CFU of Pseudomonas aeruginosa also caused persistent infection for 6 days,with large amounts of pus observed 3 days after inoculation.These models were used to evaluate the efficacy of levofloxacin（LEV） and cefoperazone（CPZ）,which reduced the viable bacteria in skin to 4log10 and 5log10 CFU/100 mg tissue,respectively.The number of bacteria in graft was significantly reduced by 4log10 CFU/mL treatment compared to the untreated group（P0.05）.These results suggest that two bacterial infection models were successfully established in tree shrew using P.aeruginosa and S.aureus.In addition,tree shrew was susceptible to P.aeruginosa and S.aureus,thus making it an ideal bacterial infection animal model for the evaluation of new antimicrobials.
文摘鉴于原猿类的树鼩在进化中的特殊地位,有关它的神经生物学研究十分活跃。树鼩的单位放电研究已有报告(J. E. Abano et al. 1978;A. L. Humphrey et al. 1977、1980),但是采用慢性微电极技术记录行为状态的树鼩的单位放电方法迄今未见报道,本文报告一种记录清醒活动状态树鼩的单位放电技术考虑到树鼩形体甚小、体重仅100多克。要分离单位放电,必须拥有一种特殊规格的微型微推进器,以适应特殊实验之需。本研究设计一种采用差动结构原理实现微推进的装置,整个装置由微推进器与基座组成。微推进器的参数如下:重量8.8克;微调范围:2.0毫米;微调读数5微米;微调可控范围:小于2微米;外形尺寸:13×13×51毫米。微推进器相对于基座有直径为1.8毫米的径向偏心移动范围。基座重0.65克,实验在局麻下,在立体定向仪控制下埋植基座。术后第二天即可实验观察。
基金supported by the grant of the National Natural Science Foundation of China(NSFC U1402224)the Chinese Academy of Sciences(CAS zsys-02)
文摘The Chinese tree shrew （Tupaia belangeri chinensis） a squirrel-like and rat-sized mammal, has a wide distribution in Southeast Asia, South and Southwest China and has many unique characteristics that make it suitable for use as an experimental animal. There have been many studies using the tree shrew （Tupaia belangeri） aimed at increasing our understanding of fundamental biological mechanisms and for the modeling of human diseases and therapeutic responses. The recent release of a publicly available annotated genome sequence of the Chinese tree shrew and its genome database （www.treeshrewdb.org） has offered a solid base from which it is possible to elucidate the basic biological properties and create animal models using this species. The extensive characterization of key factors and signaling pathways in the immune and nervous systems has shown that tree shrews possess both conserved and unique features relative to primates. Hitherto, the tree shrew has been successfully used to create animal models for myopia, depression, breast cancer, alcohol-induced or non-alcoholic fatty liver diseases, herpes simplex virus type 1 （HSV-1） and hepatitis C virus （HCV） infections, to name a few. The recent successful genetic manipulation of the tree shrew has opened a new avenue for the wider usage of this animal in biomedical research. In this opinion paper, I attempt to summarize the recent research advances that have used the Chinese tree shrew, with a focus on the new knowledge obtained by using the biological properties identified using the tree shrew genome, a proposal for the genome-based approach for creating animal models, and the genetic manipulation of the tree shrew. With more studies using this species and the application of cutting-edge gene editing techniques, the tree shrew will continue to be under the spot light as a viable animal model for investigating the basis of many different human diseases.
基金supported by the National Nature Science Foundation of China(81325016,U1602221,81322038 and U1502222)
文摘The tree shrew （Tupaia belangeri） is a promising laboratory animal that possesses a closer genetic relationship to primates than to rodents. In addition, advantages such as small size, easy breeding, and rapid reproduction make the tree shrew an ideal subject for the study of human disease. Numerous tree shrew disease models have been generated in biological and medical studies in recent years. Here we summarize current tree shrew disease models, including models of infectious diseases, cancers, depressive disorders, drug addiction, myopia, metabolic diseases, and immune-related diseases. With the success of tree shrew transgenic technology, this species will be increasingly used in biological and medical studies in the future.
基金supported by grants from Chinese Academy of Sciences (Nos.KSCX2-EW-R-11 and KSCX2-EW-J-23)the National 863 Project of China (No.2012AA021801)Yunnan Province (No.2009CI119)
文摘Tree shrew （Tupaia belangeri） is currently placed in Order Scandentia and has a wide distribution in Southeast Asia and Southwest China. Due to its unique characteristics, such as small body size, high brain-to-body mass ratio, short reproductive cycle and life span, and low-cost of maintenance, tree shrew has been proposed to be an alternative experimental animal to primates in biomedical research. However, there are some debates regarding the exact phylogenetic affinity of tree shrew to primates. In this study, we determined the mtDNA entire genomes of three Chinese tree shrews （T. belangeri chinensis） and one Malayan flying lemur （Galeopterus variegatus）. Combined with the published data for species in Euarchonta, we intended to diseen] the phylogenetic relationship among representative species of Dermoptera, Scandentia and Primates. The mtDNA genomes of Chinese tree shrews and Malayan flying lemur shared similar gene organization and structure with those of other mammals. Phylogenetic analysis based on 12 concatenated mitochondrial proteinencoding genes revealed a closer relationship between species of Scandentia and Glires, whereas species of Dermoptera were clustered with Primates. This pattern was consistent with previously reported phylogeny based on mtDNA data, but differed from the one reconstructed on the basis of nuclear genes. Our result suggested that the matrilineal affinity of tree shrew to primates may not be as close as we had thought. The ongoing project for sequencing the entire genome of Chinese tree shrew will provide more information to clarify this important issue.
基金This study was supported by the National Natural Science Foundation of China(U1902215 to Y.G.Y.and 31970542 to Y.F.)Chinese Academy of Sciences(Light of West China Program xbzg-zdsys-201909 to Y.G.Y.)Yunnan Province(202001AS070023 and 2018FB046 to D.D.Y.and 202002AA100007 to Y.G.Y.)。
文摘The Chinese tree shrew(Tupaia belangeri chinensis)is emerging as an important experimental animal in multiple fields of biomedical research.Comprehensive reference genome annotation for both mRNA and long non-coding RNA(lncRNA)is crucial for developing animal models using this species.In the current study,we collected a total of 234 high-quality RNA sequencing(RNA-seq)datasets and two long-read isoform sequencing(ISO-seq)datasets and improved the annotation of our previously assembled high-quality chromosomelevel tree shrew genome.We obtained a total of 3514 newly annotated coding genes and 50576 lncRNA genes.We also characterized the tissuespecific expression patterns and alternative splicing patterns of mRNAs and lncRNAs and mapped the orthologous relationships among 11 mammalian species using the current annotated genome.We identified 144 tree shrew-specific gene families,including interleukin 6(IL6)and STT3 oligosaccharyltransferase complex catalytic subunit B(STT3B),which underwent significant changes in size.Comparison of the overall expression patterns in tissues and pathways across four species(human,rhesus monkey,tree shrew,and mouse)indicated that tree shrews are more similar to primates than to mice at the tissue-transcriptome level.Notably,the newly annotated purine rich element binding protein A(PURA)gene and the STT3B gene family showed dysregulation upon viral infection.The updated version of the tree shrew genome annotation(KIZ version 3:TS_3.0)is available at http://www.treeshrewdb.org and provides an essential reference for basic and biomedical studies using tree shrew animal models.
基金supported by the National High-Tech R&D Program(2014ZX09102042)the National Natural Science Foundation of China(81373142)the Natural Science Foundation of Yunnan Province(2012ZA009)
文摘Coxsackie virus A16(CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease(HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and severe inflammatory CNS lesions. In this study, experimentally CA16 infected tree shrews(Tupaia belangeri) were used to investigate CA16 pathogenesis. The results showed that both the body temperature and the percentages of blood neutrophilic granulocytes / monocytes of CA16 infected tree shrews increased at 4-7 days post infection. Dynamic distributions of CA16 in different tissues and stools were found at different infection stages. Moreover, the pathological changes in CNS and other organs were also observed. These findings indicate that tree shrews can be used as a viable animal model to study CA16 infection.
