Motor development has been extensively studied in human infants and children, with several established scales for the evaluation of motor functions. However, the study of the neuronal mechanisms underlying human motor...Motor development has been extensively studied in human infants and children, with several established scales for the evaluation of motor functions. However, the study of the neuronal mechanisms underlying human motor development is hampered by the lack of good animal models. The common marmoset （Callithrix jacchus）, a small New World monkey, has recently attracted much attention as a potential non- human primate model for understanding human physiology and diseases. However, little is known about its gross motor development. In the present study, we found that marmosets have a critical period for motor development in postnatal weeks 2 to 5, and acquire most of their motor skills by 8 weeks of age. We also developed methods to assess their motor functions, which will be useful for the evaluation of motor performance in marmoset models of human diseases. In addition, we found that marmosets exhibit a ＂head-to-tail＂ sequence of motor development similar to that found in humans, further supporting the notion that they provide a good animal model for studying the neuronal mechanisms underlying human motor development.展开更多
The pygmy marmoset,the smallest of the anthropoid primates,has a broad distribution in Western Amazonia.Recent studies using molecular and morphological data have identified two distinct species separated by the Napo ...The pygmy marmoset,the smallest of the anthropoid primates,has a broad distribution in Western Amazonia.Recent studies using molecular and morphological data have identified two distinct species separated by the Napo and Solimoes-Amazonas rivers.However,reconciling this new biological evidence with current taxonomy,i.e.,two subspecies,Cebuella pygmaea pygmaea(Spix,1823)and Cebuella pygmaea niveiventris(Lönnberg,1940),was problematic given the uncertainty as to whether Spix’s pygmy marmoset(Cebuella pygmaea pygmaea)was collected north or south of the Napo and Solimoes-Amazonas rivers,making it unclear to which of the two newly revealed species the name pygmaea would apply.Here,we present the first molecular data from Spix’s type specimen of Cebuella pygmaea,as well as novel mitochondrial genomes from modern pygmy marmosets sampled near the type locality(Tabatinga)on both sides of the river.With these data,we can confirm the correct names of the two species identified,i.e.,C.pygmaea for animals north of the Napo and Solimoes-Amazonas rivers and C.niveiventris for animals south of these two rivers.Phylogenetic analyses of the novel genetic data placed into the context of cytochrome b gene sequences from across the range of pygmy marmosets further led us to reevaluate the geographical distribution for the two Cebuella species.We dated the split of these two species to 2.54 million years ago.We discuss additional,more recent,subdivisions within each lineage,as well as potential contact zones between the two species in the headwaters of these rivers.展开更多
The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regul...The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor(CB1R),which is strongly expressed in the amygdala of non-human primates(NHPs).However,it remains largely unknown how the CB1Rs in the amygdala of NHPs regulate mental diseases.Here,we investigated the role of CB1R by knocking down the cannabinoid receptor 1(CNR1)gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA.We found that CB1R knockdown in the amygdala induced anxiety-like behaviors,including disrupted night sleep,agitated psychomotor activity in new environments,and reduced social desire.Moreover,marmosets with CB1R-knockdown had up-regulated plasma cortisol levels.These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets,and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.展开更多
The common marmoset （Callithrix jacchus） has attracted extensive attention for use as a non-human primate model in biomedical research, especially in the study of neuropsychiatric disorders. However, behavioral test...The common marmoset （Callithrix jacchus） has attracted extensive attention for use as a non-human primate model in biomedical research, especially in the study of neuropsychiatric disorders. However, behavioral test methods are still limited in the field of marmoset research. The light-dark box is widely used for the evaluation of anxiety in rodents, but little is known about light-dark preference in marmosets. Here, we modified the light-dark test to study this behavior. The modified apparatus consisted of three compartments： one transparent open area and two closed opaque compartments. The closed compartments could be dark or light. We found that both adult and young marmosets liked to explore the open area, but the young animals showed more interest than adults. Furthermore, when one of the closed compartments was light and the other dark, the adult marmosets showed a preference for the dark compartment, but the young animals had no preference. These results suggest that the exploratory behavior and the light-dark preference in marmosets are age-dependent. Our study provides a new method to study exploration, anxiety, and fear in marmosets.展开更多
The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independ...The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.展开更多
The physiological characteristics of the marmoset second visual area(V2) are poorly understood compared with those of the primary visual area(V1). In this study, we observed the physiological response characteristics ...The physiological characteristics of the marmoset second visual area(V2) are poorly understood compared with those of the primary visual area(V1). In this study, we observed the physiological response characteristics of V2 neurons in four healthy adult marmosets using intracortical tungsten microelectrodes. We recorded 110 neurons in area V2, with receptive fields located between 8° and 15° eccentricity. Most(88.2%) of these neurons were orientation selective, with half-bandwidths typically ranging between 10° and 30°. A significant proportion of neurons(28.2%) with direction selectivity had a direction index greater than 0.5. The vast majority of V2 neurons had separable spatial frequency and temporal frequency curves and, according to this criterion, they were not speed selective. The basic functional response characteristics of neurons in area V2 resemble those found in area V1. Our findings show that area V2 together with V1 are important in primate visual processing, especially in locating objects in space and in detecting an object's direction of motion. The methods used in this study were approved by the Monash University Animal Ethics Committee, Australia(MARP 2009-2011) in 2009.展开更多
The common marmoset (Callithrix jacchus), a small new world monkey species, has been widely used in various scientific fields. It is necessary to understand connections between specific genotypes, their structure, and...The common marmoset (Callithrix jacchus), a small new world monkey species, has been widely used in various scientific fields. It is necessary to understand connections between specific genotypes, their structure, and function;however, an anatomical atlas of the entire body of the common marmoset has not yet been reported. In addition to conventional absorption, refraction enhanced computed tomography (CT) based on synchrotron radiation can increase the contrast of boundaries between small absorption differences. In this study, to examine the potential of creating an anatomical atlas of the whole body of the common marmoset non-invasively, we visualized an intact marmoset using synchrotron refraction enhanced CT. The cryogenic marmoset was scanned using the medical imaging beamline at the SPring-8 synchrotron radiation research facility in JAPAN. The trabecular structure, articular cartilage, cruciate ligament in the knee joint, and small airways (diameter: > 400 μm) was clearly identified with 50 μm voxel size and 37 keV x-ray energy. The structure of the heart and branching vessels in the kidneys and liver were also identified without contrast agents, and the anatomical structure of the brain was slightly visible. These results show that synchrotron refraction enhanced CT is useful for creating an anatomical atlas non-invasively, and further studies are planned that will combine refraction enhanced CT and other imaging techniques to analyse the morphology and create a complete atlas of the whole body of the common marmoset.展开更多
Mouse and non-human primate models of neurodegenerative disease：The prevalence of age-related neurodegenerative diseases continues to increase with ever increasing aging population over the age of 60.Although the dif...Mouse and non-human primate models of neurodegenerative disease：The prevalence of age-related neurodegenerative diseases continues to increase with ever increasing aging population over the age of 60.Although the difficulties associated with neurodegenerative diseases present an urgent global issue,there is no effective treatment for these conditions.展开更多
Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic intervention.In this study, we attempted to develop a leukemia...Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic intervention.In this study, we attempted to develop a leukemia nonhuman primate model that mimics various human systems. Hematopoietic stem/progenitor cells in the common marmoset were transduced with a lentiviral vector containing the p190 BCR-ABL fusion gene by ex vivo transduction or in vivo direct bone marrow injection. In the latter model, BCR-ABL gene expression was maintained for more than one and a half years. One marmoset unexpectedly developed myelofibrosis-like disease. However, none of the marmosets have developed leukemia to date. In conclusion, we successfully achieved sustained p190 BCR-ABL gene expression in vivo. However, a genetic mutation in addition to p190 BCR-ABL may be required for the malignant transformation of hematopoietic stem/progenitor cells in the common marmoset during the short observation period. This novel in vivo approach will help develop a marmoset leukemia model in the future.展开更多
基金supported by the Youth Innovation Promotion Association of the Chinese Academy of Sciences and an SA-SIBS scholarship to NGthe MoST 973 Program of China (2011CBA00400)the Strategic Priority Research Program of the CAS (XDB02020100)
文摘Motor development has been extensively studied in human infants and children, with several established scales for the evaluation of motor functions. However, the study of the neuronal mechanisms underlying human motor development is hampered by the lack of good animal models. The common marmoset （Callithrix jacchus）, a small New World monkey, has recently attracted much attention as a potential non- human primate model for understanding human physiology and diseases. However, little is known about its gross motor development. In the present study, we found that marmosets have a critical period for motor development in postnatal weeks 2 to 5, and acquire most of their motor skills by 8 weeks of age. We also developed methods to assess their motor functions, which will be useful for the evaluation of motor performance in marmoset models of human diseases. In addition, we found that marmosets exhibit a ＂head-to-tail＂ sequence of motor development similar to that found in humans, further supporting the notion that they provide a good animal model for studying the neuronal mechanisms underlying human motor development.
基金This study was supported by the Conselho Nacional de Pesquisa,Brazil(563348/2010)Coordenacao de Aperfeicoamento de Pessoal de Nível Superior(3261/2013)+2 种基金NSF(1241066)FAPESP(12/50260-6)NERC(NE/T000341/1)。
文摘The pygmy marmoset,the smallest of the anthropoid primates,has a broad distribution in Western Amazonia.Recent studies using molecular and morphological data have identified two distinct species separated by the Napo and Solimoes-Amazonas rivers.However,reconciling this new biological evidence with current taxonomy,i.e.,two subspecies,Cebuella pygmaea pygmaea(Spix,1823)and Cebuella pygmaea niveiventris(Lönnberg,1940),was problematic given the uncertainty as to whether Spix’s pygmy marmoset(Cebuella pygmaea pygmaea)was collected north or south of the Napo and Solimoes-Amazonas rivers,making it unclear to which of the two newly revealed species the name pygmaea would apply.Here,we present the first molecular data from Spix’s type specimen of Cebuella pygmaea,as well as novel mitochondrial genomes from modern pygmy marmosets sampled near the type locality(Tabatinga)on both sides of the river.With these data,we can confirm the correct names of the two species identified,i.e.,C.pygmaea for animals north of the Napo and Solimoes-Amazonas rivers and C.niveiventris for animals south of these two rivers.Phylogenetic analyses of the novel genetic data placed into the context of cytochrome b gene sequences from across the range of pygmy marmosets further led us to reevaluate the geographical distribution for the two Cebuella species.We dated the split of these two species to 2.54 million years ago.We discuss additional,more recent,subdivisions within each lineage,as well as potential contact zones between the two species in the headwaters of these rivers.
基金supported by the Zhejiang Province Natural Science Foundation of China(LD22H090003)Key-Area Research and Development Program of Guangdong Province(2019B030335001 and 2018B030334001)+3 种基金the National Natural Science Foundation of China(31871070,82090031,32071097,31871056,and 32170991)the Key R&D Program of Zhejiang Province(2020C03009)Fundamental Research Funds for the Central Universities(2021FZZX001-37)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-057).
文摘The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regulating emotions and mainly functions through the cannabinoid type-1 receptor(CB1R),which is strongly expressed in the amygdala of non-human primates(NHPs).However,it remains largely unknown how the CB1Rs in the amygdala of NHPs regulate mental diseases.Here,we investigated the role of CB1R by knocking down the cannabinoid receptor 1(CNR1)gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA.We found that CB1R knockdown in the amygdala induced anxiety-like behaviors,including disrupted night sleep,agitated psychomotor activity in new environments,and reduced social desire.Moreover,marmosets with CB1R-knockdown had up-regulated plasma cortisol levels.These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets,and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.
基金supported by the Youth Innovation Promotion Association of the Chinese Academy of Sciences and an SA-SIBS scholarshipthe National Basic Research Development Program (973 Program) of China (2011CBA00400)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB02020100)
文摘The common marmoset （Callithrix jacchus） has attracted extensive attention for use as a non-human primate model in biomedical research, especially in the study of neuropsychiatric disorders. However, behavioral test methods are still limited in the field of marmoset research. The light-dark box is widely used for the evaluation of anxiety in rodents, but little is known about light-dark preference in marmosets. Here, we modified the light-dark test to study this behavior. The modified apparatus consisted of three compartments： one transparent open area and two closed opaque compartments. The closed compartments could be dark or light. We found that both adult and young marmosets liked to explore the open area, but the young animals showed more interest than adults. Furthermore, when one of the closed compartments was light and the other dark, the adult marmosets showed a preference for the dark compartment, but the young animals had no preference. These results suggest that the exploratory behavior and the light-dark preference in marmosets are age-dependent. Our study provides a new method to study exploration, anxiety, and fear in marmosets.
基金supported by the National Natural Science Foundation of China (82001372)National Key Research and Development Program of China (2018YFE0126700)+3 种基金Shanghai Jiao Tong University 2030 Initiative (WH510363001-7)Shanghai Municipal Commission of Science and Technology Program (21dz2210100)Shanghai Education Commission Research and Innovation Program (2019-01-07-00-02-E00037)a National Institutes of Health (NIH)grant (5R01HG002385)to E.E.E。
文摘The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.
基金supported by travel grants from Monash University and the University of Sichuan(to YY)Research Grants from the Australian Research Council(No.DP0451206)(to MGPR)National Health and Medical Research Council(No.384115)(to MGPR)。
文摘The physiological characteristics of the marmoset second visual area(V2) are poorly understood compared with those of the primary visual area(V1). In this study, we observed the physiological response characteristics of V2 neurons in four healthy adult marmosets using intracortical tungsten microelectrodes. We recorded 110 neurons in area V2, with receptive fields located between 8° and 15° eccentricity. Most(88.2%) of these neurons were orientation selective, with half-bandwidths typically ranging between 10° and 30°. A significant proportion of neurons(28.2%) with direction selectivity had a direction index greater than 0.5. The vast majority of V2 neurons had separable spatial frequency and temporal frequency curves and, according to this criterion, they were not speed selective. The basic functional response characteristics of neurons in area V2 resemble those found in area V1. Our findings show that area V2 together with V1 are important in primate visual processing, especially in locating objects in space and in detecting an object's direction of motion. The methods used in this study were approved by the Monash University Animal Ethics Committee, Australia(MARP 2009-2011) in 2009.
文摘The common marmoset (Callithrix jacchus), a small new world monkey species, has been widely used in various scientific fields. It is necessary to understand connections between specific genotypes, their structure, and function;however, an anatomical atlas of the entire body of the common marmoset has not yet been reported. In addition to conventional absorption, refraction enhanced computed tomography (CT) based on synchrotron radiation can increase the contrast of boundaries between small absorption differences. In this study, to examine the potential of creating an anatomical atlas of the whole body of the common marmoset non-invasively, we visualized an intact marmoset using synchrotron refraction enhanced CT. The cryogenic marmoset was scanned using the medical imaging beamline at the SPring-8 synchrotron radiation research facility in JAPAN. The trabecular structure, articular cartilage, cruciate ligament in the knee joint, and small airways (diameter: > 400 μm) was clearly identified with 50 μm voxel size and 37 keV x-ray energy. The structure of the heart and branching vessels in the kidneys and liver were also identified without contrast agents, and the anatomical structure of the brain was slightly visible. These results show that synchrotron refraction enhanced CT is useful for creating an anatomical atlas non-invasively, and further studies are planned that will combine refraction enhanced CT and other imaging techniques to analyse the morphology and create a complete atlas of the whole body of the common marmoset.
文摘Mouse and non-human primate models of neurodegenerative disease：The prevalence of age-related neurodegenerative diseases continues to increase with ever increasing aging population over the age of 60.Although the difficulties associated with neurodegenerative diseases present an urgent global issue,there is no effective treatment for these conditions.
文摘Patients with Philadelphia chromosome (p190 BCR-ABL fusion gene)-positive acute lymphoblastic leukemia have a poor prognosis despite intensive therapeutic intervention.In this study, we attempted to develop a leukemia nonhuman primate model that mimics various human systems. Hematopoietic stem/progenitor cells in the common marmoset were transduced with a lentiviral vector containing the p190 BCR-ABL fusion gene by ex vivo transduction or in vivo direct bone marrow injection. In the latter model, BCR-ABL gene expression was maintained for more than one and a half years. One marmoset unexpectedly developed myelofibrosis-like disease. However, none of the marmosets have developed leukemia to date. In conclusion, we successfully achieved sustained p190 BCR-ABL gene expression in vivo. However, a genetic mutation in addition to p190 BCR-ABL may be required for the malignant transformation of hematopoietic stem/progenitor cells in the common marmoset during the short observation period. This novel in vivo approach will help develop a marmoset leukemia model in the future.
