LAMININ ALPHA 2 IN TISSUE REGENERATION

层粘连蛋白 ALPHA 2 在组织再生中的作用

• 批准号: 6363394
• 负责人: EVA S ENGVALL
• 金额: $ 35.17万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6363394
• 关键词: Schwann cells; affinity chromatography; cell differentiation; disease /disorder model; gene expression; gene targeting; genetic models; genetically modified animals; integrins; laboratory mouse; laminin; model design /development; muscle proteins; muscular dystrophy; mutant; myogenesis; nervous system regeneration; peripheral nervous system; phenotype; protein isoforms; protein localization; protein structure function; regeneration; striated muscles; yeast two hybrid system

DESCRIPTION: (Adapted from applicant's abstract) Tissue regeneration and repair are critical to longevity. Insufficient regeneration of muscle and nerve is a significant cause of morbidity in patients with muscular dystrophy and other muscle and nerve diseases and in the aging individual. The laminin subunit a2 is prominently expressed in striated muscle and peripheral nerve, and mutations in the lama2 gene cause a severe form of muscular dystrophy in humans (merosin-deficient congenital muscular dystrophy, MCMD) and mice. A mouse model for human MCMD was generated by disrupting the lama2 gene with the lacZ reporter gene. Homozygous mutant mice develop muscular dystrophy and peripheral neuropathy after birth. Absence of laminin a2 does not significantly affect myogenesis, but the differentiated laminin a2-deficient muscle are highly susceptible to injury upon contraction. Most important, in contrast to the apparent normal development, regeneration is severely compromised in the absence of laminin a2. It is proposed to use in vivo and in vitro models to analyze development and regeneration of skeletal muscle and peripheral nerve to determine which steps in the regeneration process are dependent on laminin a2. The regeneration-promoting effects of laminin a2 will be analyzed in transgenic mice with tissue-specific overexpression of a human LAMA2 transgene. To analyze the molecular pathways responsible for maturation and survival of skeletal muscle and Schwann cells, integrin and dystroglycan signaling pathways will be characterized by using the yeast 2-hybrid screening and affinity chromatography in combination with peptide mass mapping. The proposed research will result in new knowledge regarding important molecular mechanisms of muscle and nerve function and may help in devising new strategies for treatment of degenerative diseases of muscle and nerve based on promoting regeneration.

描述：（改编自申请人摘要）组织再生与修复