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Apolipoprotein E4 interferes with lipid metabolism to exacerbate depression-like behaviors in 5xFAD mice

animal models and Experimental Medicine 2024年第3期7卷 347-361页

作者： Yanju Gong Mingfeng Li Min Liu Xinghan Wu Yanhong Li Chuan Qin Ling Zhang iNHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInternational Center for Technology and lnnovation of Animal ModelComparative Medicine CenterInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PuMC)BeijingChina Changping national Laboratory(CPNL) BeijingChina

Background:Apolipoprotein E4(ApoE4)allele is the strongest genetic risk factor for late-onset Alzheimer's disease,and it can aggravate depressive symptoms in non-AD ***,the impact of ApoE4 on AD-associated depression-l ike behaviors and its underlying pathogenic mechanisms remain ***:This study developed a 5xFAD mouse model overexpressing human ApoE4(E4FAD).Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD *** in peripheral and central lipid metabolism,as well as the levels of serotonin(5-HT)andγ-aminobutyric acid(GABA)neurotransmitters in the prefrontal cortex,were *** addition,the protein levels of 24-dehydrocholesterol reductase/glycogen synthase kinase-3 beta/mammalian target of rapamycin(DHCR24/GSK3β/m TOR)and postsynaptic density protein 95/calmodulin-dependent protein kinase II/brain-derived neurotrophic factor(PSD95/CaMK-II/BDNF)were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD ***:Compared with 5xFAD mice,E4FAD mice exhibited more severe depressionlike behaviors and cognitive *** mice also exhibited increased amyloid-beta deposition in the hippocampus,increased astrocyte numbers,and decreased expression of depression-related neurotransmitters 5-HT and GABA in the prefrontal ***,lipid metabolism disorders were observed in E4FAD,manifesting as elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol in peripheral blood,decreased cholesterol level in the prefrontal cortex,and reduced expression of key enzymes and proteins related to cholesterol synthesis and *** expression of proteins related to the DHCR24/GSK3β/m TOR and PSD95/CaMK-II/BDNF pathways was also ***:This study found that ApoE4 overexpression exacerbates depressionlike behaviors in 5xFAD mice and confirmed that ApoE4 reduces co

关键词： 5xFAD mice Alzheimer's disease ApoE4 allele depression like

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B cell development and antibody responses in human immune system mice:current status and future perspective

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Science China(Life Sciences) 2024年第4期67卷 645-652页

作者： Tao Zhang Wentao Liu Yong-Guang Yang Key Laboratory of Organ Regeneration&Transplantation of the Ministry of Education The First Hospital of Jilin UniversityChangchun 130061China national-Local Joint Engineering Laboratory of animal models for Human Diseases Jilin UniversityChangchun 130061China international center of Future Science Jilin UniversityChangchun 130061China

Humanized immune system(HIS)mice have been developed and used as a small surrogate model to study human immune function under normal or disease *** variations are found between models,most HIS mice show robust human T cell ***,there has been unsuccessful in constructing HIS mice that produce high-affinity human antibodies,primarily due to defects in terminal B cell differentiation,antibody affinity maturation,and development of primary follicles and germinal *** this review,we elaborate on the current knowledge about and previous attempts to improve human B cell development in HIS mice,and propose a potential strategy for constructing HIS mice with improved humoral immunity by transplantation of human follicular dendritic cells(FDCs)to facilitate the development of secondary follicles.

关键词： humanized immune system mouse humoral immunity germinal center B cell follicular dendritic cell

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Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational Medical research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The national Clinical research center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain *** this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2 processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

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Growth performance,serum parameters,inflammatory responses,intestinal morphology and microbiota of weaned piglets fed 18%crude protein diets with different ratios of standardized ileal digestible isoleucine to lysine

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animal Nutrition 2024年第1期16卷 313-325页

作者： Jian Wang Sujie Liu Jiayu Ma Xiaoli Dong Shenfei Long Xiangshu Piao State Key Laboratory of animal Nutrition College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Beijing Jingwa Agricultural Science and Technology Innovation center Beijing101206China CJ international Trading Co. LtdShanghai 201107China

The present study was to explore the Ile requirement of piglets fed 18%crude protein(CP)*** hundred and fifty 28-day-old Duroc×Landrace×Yorkshire piglets(8.37±1.92 kg)were randomly divided into 5 dietary treatments(10 piglets per replicate,5 barrows and 5 gilts per replicate)with 45%,50%,55%,60%,65%standardized ileal digestible(SID)Ile-to-Lys ratios,and the SID Lys was formulated to1.19%.The experimental design consisted of two phases(d 1 to 14 and d 15 to 28).Results showed that average daily gain(ADG)had a tendency to quadratically increase as the SID Ile-to-Lys ratio increased(P=0.09),and the optimum SID Ile-to-Lys ratios required to maximize ADG were 48.33%and 54.63%for broken-line linear model and quadratic polynomial model,*** SID Ile-to-Lys ratios had no significant effects on average daily feed intake and gain-to-feed *** matter(Pmodels,respectively,and the deficiency or excess of lle negative

关键词： Weaned piglet Growth performance Intestinal health Isoleucine Reduced crude protein diet

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Comparative transcriptome analysis between rhesus macaques(Macaca mulatta) and crab-eating macaques(M. fascicularis)

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Zoological research 2024年第2期45卷 299-310页

作者： Yu-Xiang Mao Yamei Li Zikun Yang Ning Xu Shilong Zhang Xuankai Wang Xiangyu Yang Qiang Sun Yafei Mao Institute of Neuroscience State Key Laboratory of NeuroscienceCenter for Excellence in Brain Science&Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Shanghai center for Brain Science and Brain-Inspired Intelligence Technology Shanghai 201210China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Genetic Evolution&animal models Chinese Academy of SciencesKunmingYunnan 650201China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric DisordersMinistry of EducationShanghai Jiao Tong UniversityShanghai 200030China Zhiyuan College Shanghai Jiao Tong UniversityShanghai 200240China center for Genomic research International Institutes of MedicineFourth Affiliated HospitalZhejiang UniversityYiwuZhejiang 322000China

Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from84 samples(41 MFA samples and 43 MMU samples)encompassing 14 common tissues. Our findings revealed a small fraction of genes(3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover,19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary,this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.

关键词： Crab-eating macaques Rhesus macaques Comparative transcriptomics Biomedical models Nonhuman primates RNA-seq Duplicated genes

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Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways

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animal models and Experimental Medicine 2024年第3期7卷 208-221页

作者： Da-zhuang Lu Li-jun Zeng Yang Li Ran-li Gu Meng-long Hu Ping Zhang Peng Yu Xiao Zhang Zheng-wei Xie Hao Liu Yong-sheng Zhou Department of Prosthodontics Peking University School and Hospital of StomatologyBeijingChina national center of Stomatology BeijingChina national Clinical research center for Oral Diseases BeijingChina Beijing Key Laboratory of Digital Stomatology BeijingChina Department of Cariology and Endodontology Peking University School and Hospital of StomatologyBeijingChina Peking University international Cancer Institute Peking University Health Science CenterPeking UniversityBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina national Engineering research center of Oral Biomaterials and Digital Medical Devices BeijingChina

Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone ***,current anti-resorptive drugs carry a risk of various *** deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression *** study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone ***:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary ***-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also *** underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),***:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of *** BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting ***:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.

关键词： BMPs/SMAD bone loss cinobufotalin hBMMSCs osteogenesis osteoporosis Wnt/β-catenin signaling pathways

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Infection with SARS-CoV-2 can cause pancreatic impairment

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2143-2160页

作者： Wei Deng Linlin Bao Zhiqi Song Ling Zhang Pin Yu Yanfeng Xu Jue Wang Wenjie Zhao Xiuqin Zhang Yunlin Han Yanhong Li Jiangning Liu Qi Lv Xujian Liang Fengdi Li Feifei Qi Ran Deng Siyuan Wang Yibai Xiong Ruiping Xiao Hongyang Wang Chuan Qin NHC Key Laboratory of Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China Institute of Molecular Medicine College of Future TechnologyPeking UniversityBeijing 100871China Beijing Key Laboratory of Cardiometabolic Molecular Medicine Peking UniversityBeijing 100871China State Key Laboratory of Biomembrane and Membrane Biotechnology Peking-Tsinghua Center for Life SciencesBeijing 100871China Chinese Academy of Engineering Eastern Hepatobiliary Surgery Hospital225 Changhai RoadYangpu DistrictShanghai 200438China international Co-operation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438PR China national Laboratory for Oncogenes and Related Genes Cancer Institute of Shanghai Jiao Tong UniversityShanghai 200441PR China Changping national laboratory(CPNL) Beijing 102206China State Key Laboratory of Respiratory Health and Multimorbidity National Health Commission of the People’s Republic of ChinaBeijingPR China

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of ***,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 ***-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and *** and limited phenotypic and histopathological changes were observed in adult *** proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio ***,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic *** contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

关键词： infected elevated homeostasis

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Study of tree shrew biology and models: A booming and prosperous field for biomedical research

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Zoological research 2024年第4期45卷 877-909页

作者： Yong-Gang Yao Li Lu Rong-Jun Ni Rui Bi Ceshi Chen Jia-Qi Chen Eberhard Fuchs Marina Gorbatyuk Hao Lei Hongli Li Chunyu Liu Long-Bao Lv Kyoko Tsukiyama-Kohara Michinori Kohara Claudia Perez-Cruz Gregor Rainer Bao-Ci Shan Fang Shen An-Zhou Tang Jing Wang Wei Xia Xueshan Xia Ling Xu Dandan Yu Feng Zhang Ping Zheng Yong-Tang Zheng Jumin Zhou Jiang-Ning Zhou Key Laboratory of Genetic Evolution and animal models Yunnan Key Laboratory of Animal Models and Human Disease MechanismsKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China national research Facility for Phenotypic&Genetic Analysis of Model animals(Primate Facility) and National Resource Center for Non-Human PrimatesKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China KIZ-CUHK Joint Laboratory of Bioresources and Molecular research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China Mental Health center and Psychiatric Laboratory West China HospitalSichuan UniversityChengduSichuan 610041China Sichuan Clinical Medical research center for Mental Disorders ChengduSichuan 610044China German Primate center Leibniz Institute of Primate ResearchGöttingen 37077Germany Department of Optometry and Vision Science School of OptometryUniversity of Alabama at BirminghamBirminghamAL 35294USA State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Innovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Wuhan national Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Transboundary animal Diseases center Joint Faculty of Veterinary MedicineKagoshima UniversityKagoshima-cityKagoshima 890-8580Japan Department of Microbiology and Cell Biology Tokyo Metropolitan Institute of Medical ScienceTokyo 156-8506Japan Pharmacology Department CinvestavMexico City 07360Mexico Department of Medicine University of FribourgFribourg CH-1700Switzerland Beijing Engineering research center of Radiog

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 *** 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 ***,the limited availability of tree shrews globally remains a substantial challenge in the ***,determining the key questions best answered using tree shrews constitutes another *** 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 *** these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical *** review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this *** emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew *** 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.

关键词： Tree shrew animal model Neurodegenerative diseases Infectious diseases Neuroscience Phenome

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Liver-specific Deletion of Growth Hormone Receptor Induced the Pathogenesis of Nonalcoholic Steatohepatitis

Liver-specific Deletion of Growth Hormone Receptor Induced t...

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第三届中国生物物理学会代谢生物学分会学术研讨会

作者： Rujiao Jiang Xiaoxin Wang Dong Yu Zicheng Pu Meijun Jiang Yingjie Wu Institute of Genome engineered animal models for Human Diseases National Center of Genetically Engineered Animal Models for International ResearchCollege （Institute） of Integrative Medicine.Dalian Medical University

＜正＞On the spectrum of the nonalcoholic fatty liver diseases （NAFLD）,nonalcoholic steatohepatitis（NASH） is a progressive condition when inflammation,fibrosis and liver cell damage developed from simple *** NASH only occurs in a small subset of NAFLD patients,it poses a high risk to progress to liver cirrhosis,liver failure and hepatocellular *** is considered to be the liver manifestation of metabolic syndrome,but other systems such as adipose

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Unraveling the complexity of polycystic ovary syndrome with animal models

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Journal of Genetics and Genomics 2024年第2期51卷 144-158页

作者： Huanju Liu Mixue Tu Zhiyong Yin Dan Zhang Jun Ma Feng He center for Genetic Medicine The Fourth Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China Key Laboratory of Women's Reproductive Health of Zhejiang Province and Department of Reproductive Endocrinology Women's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China Zhejiang Provincial Clinical research center for Child Health Women's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China Clinical research center on Birth Defect Prevention and Intervention of Zhejiang Province HangzhouZhejiang 310006China Institute of Genetics Zhejiang University International School of MedicineHangzhouZhejiang 310058China Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorder HangzhouZhejiang 310058China

Polycystic ovary syndrome (PCOS) is a highly familial and heritable endocrine disorder. Over half of the daughters born to women with PCOS may eventually develop their own PCOS-related symptoms. Progress in the treatment of PCOS is currently hindered by the complexity of its clinical manifestations and incomplete knowledge of its etiopathogenesis. Various animal models, including experimentally induced, naturally occurring, and spontaneously arising ones, have been established to emulate a wide range of phenotypical and pathological traits of human PCOS. These studies have led to a paradigm shift in understanding the genetic, developmental, and evolutionary origins of this disorder. Furthermore, emerging evidence suggests that animal models are useful in evaluating state-of-the-art drugs and treatments for PCOS. This review aims to provide a comprehensive summary of recent studies of PCOS in animal models, highlighting the power of these disease models in understanding the biology of PCOS and aiding high-throughput approaches.

关键词： Polycystic ovary syndrome animal model Genetc manipulation Developmnental progtanning Drug screening

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