Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly inve...Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.展开更多
Severe combined immunodeficiency(SCiD)encompasses a range of inherited disorders that lead to a profound deterioration of the immune system.Among the pivotal genes associated with SCID,RAG1 and IL2RG play crucial role...Severe combined immunodeficiency(SCiD)encompasses a range of inherited disorders that lead to a profound deterioration of the immune system.Among the pivotal genes associated with SCID,RAG1 and IL2RG play crucial roles.IL2RG is essential for the development,differentiation,and functioning of T,B,and NK cells,while RAG1 critically contributes to adaptive immunity by facilitating V(D)J recombination during the maturation of lymphocytes.Animal models carrying mutations in these genes exhibit notable deficiencies in their immune systems.展开更多
Tauopathy,characterized by the hyperphosphorylation and accumulation of the microtubule-associated protein tau,and the accumulation of Aβ oligomers,constitute the major pathological hallmarks of Alzheimer's disea...Tauopathy,characterized by the hyperphosphorylation and accumulation of the microtubule-associated protein tau,and the accumulation of Aβ oligomers,constitute the major pathological hallmarks of Alzheimer's disease.However,the relationship and causal roles of these two pathological changes in neurodegeneration remain to be defined,even though they occur together or independently in several neurodegenerative diseases associated with cognitive and movement impairment.展开更多
基金supported by the National Key Research and Development Program of China (2021YFA0805300,2021YFA0805200)National Natural Science Foundation of China (32170981,82371874,82394422,82171244,82071421,82271902)+1 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001)。
文摘Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.
基金This work was supported by the National Key Research and Development Program of China(2021YFA0805300,2021YFA0805204)the National Natural Science Foundation of China(82171244,81922026,32170981)Guangzhou Key Research Program on Brain Science(202007030008).
文摘Severe combined immunodeficiency(SCiD)encompasses a range of inherited disorders that lead to a profound deterioration of the immune system.Among the pivotal genes associated with SCID,RAG1 and IL2RG play crucial roles.IL2RG is essential for the development,differentiation,and functioning of T,B,and NK cells,while RAG1 critically contributes to adaptive immunity by facilitating V(D)J recombination during the maturation of lymphocytes.Animal models carrying mutations in these genes exhibit notable deficiencies in their immune systems.
基金This work was supported by the Guangzhou Key Research Program on Brain Science(202007030008,202007030003)The National Natural Science Foundation of China(32170981,81830032,31872779,81922026,82071421,82171244)+2 种基金National Key Research and Development Program of China(2021YFA0805300,2021YFA0805200)Department of Science and Technology of Guangdong Province(2021ZT09Y007,2020B121201006)Key Field Research and Development Program of Guangdong province(2018B030337001).
文摘Tauopathy,characterized by the hyperphosphorylation and accumulation of the microtubule-associated protein tau,and the accumulation of Aβ oligomers,constitute the major pathological hallmarks of Alzheimer's disease.However,the relationship and causal roles of these two pathological changes in neurodegeneration remain to be defined,even though they occur together or independently in several neurodegenerative diseases associated with cognitive and movement impairment.
