RANDOM MUTAGENESIS SCREEN FOR BEHAVIORAL MUTANTS IN MICE

小鼠行为突变体的随机诱变筛选

• 批准号: 6363700
• 负责人: MAJA BUCAN
• 金额: $ 32.24万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6363700
• 关键词: animal breeding; auditory stimulus; autosomal recessive trait; behavioral /social science research tag; behavioral genetics; developmental genetics; gene complementation; gene deletion mutation; gene mutation; genetic mapping; genetic models; laboratory mouse; model design /development; mutagens; neurogenetics; neuropathology; nitrosourea; phenotype; startle reaction

The long term objective of our studies is to identify novel behavioral mutations in mice which may allow the dissection of genetic pathways underlying neurobiological processes. The limited availability of appropriate animal models has hindered research in complex neuropsychiatric illnesses such as schizophrenia, major affective disorders, and sleep disorders. Pharmacologic and surgical manipulations have been used to induce behaviors that simulate aspects of human disorders in laboratory animal models; however, these models represent phenocopies and do not reflect genetic causes of aberrant behavior in the animal. The approach outlined in this proposal involves random mutagenesis of the mouse genome, using a potent mutagen N-ethyl-N nitrosourea (ENU), and screens for abnormal behavioral phenotypes; in particular, disrupted rest: activity behavior and altered acoustic startle response. Novel mutations will be phenotypically characterized based on their chromosomal location and complementation analysis. This project is part of a larger effort-NIH Investigator-Initiated Interactive Research Project (IRPG)- to perform a genome-wide search for dominant behavioral mutations and to saturate a portion of the mouse genome with recessive mutations. A combination of random mutagenesis (IRPG one proposal) with an effort to create deletions (IRPG two proposal) across the 30 cM region on mouse chromosome 5, well characterized at the genetic and molecular level, will allow the identification of recessive mutations in a two generation saturation screen for 2% of the mouse genome. The IRPG effort will allow identification, phenotypic analysis and mapping of development and behavioral mutants as well as identification of mutants whose dominant behavioral anomalies may be due to underlying development, and/or neuroanatomical and neuropathological defects.

我们研究的长期目标是确定新的行为