Factors Determining Intraocular Pressure

决定眼压的因素

• 批准号: 6860990
• 负责人: SIMON W JOHN
• 金额: $ 73.97万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6860990
• 关键词: animal genetic material tag; congenital eye disorder; gene expression; gene mutation; genetic mapping; genetic regulation; glaucoma; hemostasis; intraocular pressure; laboratory mouse; molecular cloning; neuropeptide receptor; receptor expression

DESCRIPTION (provided by applicant): Glaucoma is a leading cause of blindness. Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. Our goal is to identify and characterize genetic factors that contribute to elevated IOP and glaucoma. Specifically, we are using the mouse as a model system to conduct a phenotype driven mutagenesis screen to identify novel mechanisms and pathways involved in glaucoma pathogenesis. The power of phenotype driven mutagenesis screen is that there is no requisite a priori information for factors or pathways involved. Since little is currently known about IOP homeostasis, this method for identification of new genetic factors is ideal. We propose that in the time of this grant we will identify approximately 10 new glaucoma related mutations. This method has already provided us with one new locus (Eel) for primary congenital glaucoma that we propose to clone and a second enlarged eye mutant (Ee3) that we will characterize and fine map. A feature of our phenotype-driven screen is enrichment for mutation detection on mouse chromosome 5, in a region of conserved synteny to human chromosome 7q36. This region contains 2 human glaucoma loci for which the genetic cause is unknown. While we are able to enrich for this region of considerable interest, our method does not impede the likelihood of identifying mutations elsewhere in the genome. Therefore, mutations contributing to IOP and will be mapped and prioritized based on similarity to human glaucomatous phenotypes and known human glaucoma map positions. We predict that using the power of a phenotype driven mutagenesis screen in parallel with our unique tools to examine ocular phenotypes we will be able to identify and characterize new genetic factors that contribute to elevated IOP and advance understanding of glaucoma.

描述(申请人提供)：青光眼是导致失明的主要原因。 眼压升高是青光眼的主要危险因素。我们的 我们的目标是识别和描述导致 眼压升高和青光眼。具体地说，我们使用鼠标作为模型 系统进行表型驱动的突变筛选以识别新的 青光眼发病的机制和途径。的力量 表型驱动的突变筛选是不需要先验的 所涉及的因素或途径的信息。由于目前知之甚少 关于眼压稳态，这种识别新遗传因素的方法是 非常理想。我们建议，在这笔赠款的时间里，我们将确定大约 10个新的青光眼相关突变。这种方法已经为我们提供了一个 我们建议克隆的原发先天性青光眼的新基因座(EEL)和 第二个大眼突变体(Ee3)，我们将对其进行特征分析和精细定位。一个 我们的表型驱动筛选的特点是对突变检测进行丰富 小鼠5号染色体，位于与人类染色体7q36同源的保守区域。 该区域包含2个人类青光眼基因座，其遗传原因是 未知。虽然我们能够为这一令人感兴趣的地区进行浓缩， 我们的方法不会妨碍在其他地方发现突变的可能性 基因组。因此，导致眼压的突变将被绘制出来，并 根据与人类青光眼表型的相似性和已知的 人类青光眼地图位置。我们预测，利用表型的力量 驱动突变筛查与我们独特的眼科检查工具并行 表型我们将能够识别和表征新的遗传因素 这会导致眼压升高，并加深对青光眼的了解。