Mouse models of ZNF804A

ZNF804A鼠标型号

• 批准号: 9093082
• 负责人: BRUCE A HAMILTON
• 金额: $ 23.25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9093082
• 关键词: Address; Affinity; Alleles; Animal Model; Animals; Behavior; Binding; Biological; Biological Models; Biology; Bipolar Disorder; Brain; Code; Conserved Sequence; Data; Development; Diagnosis; Disease; Disease susceptibility; Endogenous Retroviruses; Ensure; Epitopes; Exons; Experimental Models; Face; Family; Gene Components; General Population; Genes; Genetic; Genetic Variation; Genetic study; Histology; Homologous Gene; Human; In Situ; Injection of therapeutic agent; Intervention; Introns; Maps; Mental Health; Mental disorders; Meta-Analysis; Mind; Molecular; Mus; Mutation; Open Reading Frames; Orthologous Gene; Patients; Penetrance; Phenotype; Physiological; Predisposition; Protein Isoforms; Proteins; Publications; RNA; RNA Processing; Reporting; Risk; Role; Schizophrenia; Series; Site; Structure; Study models; Testing; Thick; Validation; Variant; Zinc Fingers; base; cohort; genome editing; genome-wide; insight; interest; loss of function; mental function; model development; mouse model; neuropsychiatric disorder; neuropsychiatry; public health relevance; research study; response; risk variant; theories; trait; transcription factor; white matter

 DESCRIPTION (provided by applicant): This proposal will examine the role of Zfp804a in mouse brain development and behavior as a potential model for biological basis of psychiatric illness. Schizophrenia and other psychiatric illnesses have been recognized to have a familial component for several decades, but genes that underlie these disorders have only recently begun to be identified. In addition to a very few genes with high penetrance in rare families, consortium studies have begun to identify with high confidence larger numbers of genes whose common variants are associated with schizophrenia and bipolar disorder in the general population. While these associated variants individually have only limited predictive power for diagnosis, they nonetheless mark biological bases for the disorder. Understanding the basic mechanisms through which these genes impact brain and mental function may therefore provide key insights into risk and intervention. One of the best-supported and most-replicated associations with schizophrenia and bipolar disorder is ZNF804A, which encodes a protein with a single zinc finger motif and other conserved sequences whose functions are not known. This exploratory proposal aims to create animal models that will (1) test whether the ZNF804A homolog in mouse is required for brain development or normal behavior and (2) facilitate molecular studies to place ZNF804A in cellular and molecular context.

 描述（由申请人提供）：该提案将研究 Zfp804a 在小鼠大脑发育和行为中的作用，作为精神疾病生物学基础的潜在模型。几十年来，人们已经认识到精神分裂症和其他精神疾病具有家族因素，但导致这些疾病的基因直到最近才开始被发现。除了罕见家族中极少数具有高外显率的基因外，联合研究已开始以高置信度鉴定出大量基因，其常见变异与一般人群中的精神分裂症和躁郁症相关。虽然这些相关变异单独对诊断的预测能力有限，但它们仍然标志着该疾病的生物学基础。因此，了解这些基因影响大脑和心理功能的基本机制可能会为风险和干预提供重要的见解。 ZNF804A 与精神分裂症和双相情感障碍之间的关联得到最充分的支持和复制最多，它编码一种具有单个锌指基序和其他功能未知的保守序列的蛋白质。该探索性提案旨在创建动物模型，以（1）测试小鼠中的 ZNF804A 同源物是否是大脑发育或正常行为所必需的；（2）促进分子研究，将 ZNF804A 置于细胞和分子环境中。