The Role of IgLONS in Cardiac Development and Disease

IgLONS 在心脏发育和疾病中的作用

• 批准号: 6601875
• 负责人: PAUL David GROSSFELD
• 金额: $ 12.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6601875
• 关键词: animal genetic material tag; antisense nucleic acid; cardiogenesis; cell adhesion molecules; clinical research; congenital heart disorder; developmental genetics; family genetics; gene deletion mutation; genetic mapping; genetic models; genetic susceptibility; genetically modified animals; human genetic material tag; human subject; immunofluorescence technique; laboratory mouse; northern blottings; point mutation; protein isoforms; single nucleotide polymorphism

DESCRIPTION (provided by applicant): Dr. Grossfeld is a highly trained, board-certified pediatric cardiologist who is devoted to studying the genetic basis of congenital heart disease. The purpose of this grant proposal is to obtain support to enable Dr. Grossfeld to become an independent investigator by the end of the proposed funding period. The proposed research will be performed in the laboratory of Dr. Anthony Wynshaw-Boris in the Department of Pediatrics at the University of California, San Diego. During this time, Dr. Grossfeld will receive the necessary training for incorporating human and animal genetic model system approaches for studying genes causing hypoplastic left heart syndrome (HLHS). UCSD and specifically, Dr. Wynshaw-Boris, provide an ideal environment that has been extraordinarily successful for promoting and developing similar research interests. The long-term goal of this project is to study the role of OBCAM and Neurotrimin, two members of the IgLON subfamily of genes, in cardiac development and in the generation of congenital heart defects, including HLHS. HLHS is one of the most severe congenital heart defects, accounting for 20% of all deaths in infants with congenital heart disease. To date, no causative gene for HLHS has been reported. The specific aims of this project are: Specific Aim 1): Characterization of the expression of OBCAM and Neurotrimin in fetal and adult heart; Specific Aim 2): Alteration in the expression of OBCAM and Neurotrimin utilizing mouse and chicken genetic model systems, and Specific Aim 3): Mutation analysis for point mutations and microdeletions in OBCAM and Neurotrimin in patients with isolated heart defects that occur in Jacobsen syndrome, and for single nucleotide polymorphisms in OBCAM and Neurotrimin in patients with Jacobsen syndrome.

描述（由申请人提供）： Grossfeld 博士是一位训练有素、经过委员会认证的儿科心脏病专家，致力于研究先天性心脏病的遗传基础。 本拨款提案的目的是获得支持，使 Grossfeld 博士能够在拟议资助期结束前成为一名独立研究者。 拟议的研究将在圣地亚哥加利福尼亚大学儿科系 Anthony Wynshaw-Boris 博士的实验室中进行。 在此期间，Grossfeld 博士将接受必要的培训，以结合人类和动物遗传模型系统方法来研究导致左心发育不全综合征 (HLHS) 的基因。 加州大学圣地亚哥分校，特别是 Wynshaw-Boris 博士，提供了一个理想的环境，在促进和发展类似的研究兴趣方面取得了巨大的成功。 该项目的长期目标是研究 OBCAM 和 Neurotrimin（IgLON 基因亚家族的两个成员）在心脏发育和先天性心脏缺陷（包括 HLHS）产生中的作用。 HLHS是最严重的先天性心脏病之一，占先天性心脏病婴儿死亡总数的20%。迄今为止，尚未报道 HLHS 的致病基因。 该项目的具体目标是： 具体目标 1)：胎儿和成人心脏中 OBCAM 和 Neurotrimin 表达的表征；具体目标 2)：利用小鼠和鸡遗传模型系统改变 OBCAM 和 Neurotrimin 的表达，具体目标 3)：对患有雅各布森综合征的孤立性心脏缺陷患者的 OBCAM 和 Neurotrimin 中的点突变和微缺失进行突变分析，以及雅各布森综合征患者 OBCAM 和 Neurotrimin 的单核苷酸多态性。