Mouse models of ZNF804A

ZNF804A鼠标型号

基本信息

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
项目类别：
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

项目摘要

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，作为精神疾病的生物学基础的潜在模型，几十年来，精神分裂症和其他精神疾病已被认为具有家族因素。导致这些疾病的基因最近才开始被识别，除了罕见家族中极少数具有高外显率的基因外，联合研究已经开始以高置信度识别出大量与常见变异相关的基因。虽然这些相关变异单独对诊断的预测能力有限，但它们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最广泛的研究，它编码一种具有单个锌指基序和其他功能不具有功能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。