GENETIC STUDIES OF NON-ERYTHROID SPECTRIN

非红细胞血影蛋白的遗传学研究

• 批准号: 3296785
• 负责人: DANIEL none BRANTON
• 金额: $ 23.23万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-06-01 至 1997-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3296785
• 关键词: Drosophilidae; binding proteins; cell differentiation; chemical binding; complementary DNA; developmental genetics; electron microscopy; enzyme linked immunosorbent assay; gel electrophoresis; gene complementation; gene expression; genetic library; immunofluorescence technique; laboratory mouse; laboratory rabbit; membrane activity; molecular cloning; monoclonal antibody; mutagen testing; nucleic acid probes; nucleic acid sequence; protein structure function; restriction mapping; spectrin; temperature sensitive mutant; tissue /cell culture

Spectrin function will be analyzed in a model system, Drosophila melanogaster. Spectrin is a membrane-associated cytoskeletal protein that plays a key role in the determination of erythrocyte cell shape. spectrin also plays unknown, but essential, roles in non-erythroid cells. As a result of our recent work that has identified alpha-spectrin mutants, we are in the singular position of being able to directly assess the functions of spectrin in non-erythroid cells. Using a combination of biochemical, molecular genetic, and classical genetic analyses, we will test various hypotheses for spectrin function in non-erythroid tissue at the cellular, developmental and organismal level. Beta-spectrin mutants will be produced and these, together with recently identified alpha-spectrin mutants, will be utilized to investigate spectrin function in vivo. Phenotype analysis will determine the effects of the complete absence of functional spectrin; mosaic analysis will determine the effects of spectrin absence at selected developmental stages. This phenotype information will be used to design experiments that rescue null mutants with spectrin-DNA constructs that will test the cellular or developmental role of a specific aspect of spectrin organization, such as membrane binding, or spectrin chain- length. Although spectrin isoforms are present in nearly all human cells, the neurological and general health consequences of defective spectrin expression in non-erythroid cells are only beginning to be explored. The proposed experiments will provide an in-depth understanding of spectrin's role in non-erythroid cells.

Spectrin函数将在模型系统Drosophila中进行分析