GENETIC AND EPIGENETIC CONTROL OF EYE GROWTH

眼睛生长的遗传和表观遗传控制

• 批准号: 6658958
• 负责人: ROBERT W. WILLIAMS
• 金额: $ 28.4万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6658958
• 关键词: cornea; cryostat; developmental genetics; eye; gene environment interaction; gene expression; genetic regulation; genetically modified animals; histogenesis; image processing; laboratory mouse; lens; linkage mapping; molecular cloning; myopia; phenotype; polymerase chain reaction; quantitative trait loci; retina; video microscopy

DESCRIPTION (Adapted from applicant's abstract): Myopia is an extremely pervasive abnormality of vision that is usually caused by excessive growth of the posterior part of the eye relative to the optical power of the cornea and lens. The cumulative cost of myopia and its treatment is huge. The onset and progression of myopia are strongly influenced by environmental factors, but the risk of becoming myopic is clearly influenced by genes. The central aim of this work is to determine what genes and molecules normally regulate the growth of different parts of the mammalian eye and to then assess whether any of these same genes contribute to optical abnormality in humans. The first aim of this project is to systematically map genes that selectively influence the growth of the eye, the lens, the cornea, and the retina of mice. Using novel quantitative trait locus (QTL) interval mapping methods, more than 10 gene loci that selectively affect the growth of different parts of the eye will be mapped with F2 intercrosses. As part of the second aim, these QTLs will be mapped with far greater precision (a critical region of 1‑2 cM) using special mapping resources‑advanced intercrosses and reciprocal congenic lines. Complementary methods will then be used to evaluate the most promising candidate genes linked with particular QTLs. The third aim is a developmental study of the mekics of eye growth in several important strains, and in specially engineered congenic strains. This work will test ideas about how genes and environmental factors affect the optics of eye development. Understanding how different QTLs affect different parts of the eye will ultimately contribute to a far better understanding of molecular and developmental mechanisms associated with eye growth in humans.

描述（改编自申请人摘要）：近视是一种极端的 一种普遍的视力异常，通常是由于眼睛的过度生长引起的。 眼睛的后部相对于角膜的光焦度， 透镜。近视及其治疗的累积成本是巨大的。发病和 近视的发展受到环境因素的强烈影响，但 患近视的风险显然受到基因的影响。其核心目标是 这项工作的目的是确定哪些基因和分子通常调控着 哺乳动物眼睛的不同部位，然后评估这些 同样的基因导致了人类的视觉异常。 该项目的第一个目标是系统地绘制基因， 影响小鼠眼睛、透镜、角膜和视网膜的生长。 利用新的数量性状基因座（QTL）区间作图方法， 10个基因位点选择性地影响眼睛不同部位的生长 将与F2互交作图。作为第二个目标的一部分，这些QTL将 可以用更高的精度（1 - 2cM的关键区域）绘制， 特殊作图资源高级杂交和互作同源 线然后将使用补充方法来评估最有希望的 与特定QTL连锁的候选基因。第三个目标是发展 研究了几种重要品系的眼生长机制， 特别工程化的同类菌株。这项工作将测试的想法， 基因和环境因素影响眼睛的光学发育。 了解不同的QTL如何影响眼睛的不同部位， 最终有助于更好地理解分子和 与人类眼睛生长相关的发育机制。

项目成果

The ldis1 lens mutation in RIIIS/J mice maps to chromosome 8 near cadherin 1.

• 发表时间: 2004-08
• 期刊: Molecular vision
• 影响因子: 2.2
• 作者: M. Jablonski;Lu Lu-Lu;Xiaofei F Wang;E. Chesler;Emily Carps;Shuhua Qi;Jing Gu;Robert W. Williams

Modulation of retinal cell populations and eye size in retinoic acid receptor knockout mice.

• 发表时间: 2001-11
• 期刊: Molecular vision
• 影响因子: 2.2
• 作者: Guomin Zhou;R. C. Strom;Vincent Giguère;Robert W. Williams

Posttranscriptional regulation of the immediate-early gene EGR1 by light in the mouse retina.

小鼠视网膜中光对立即早期基因 EGR1 的转录后调节。

• DOI: 10.1111/j.1460-9568.2004.03811.x
• 发表时间: 2004
• 期刊: The European journal of neuroscience.
• 作者: Simon,Perikles;Schott,Klaus;Williams,RobertW;Schaeffel,Frank
• 通讯作者: Schaeffel,Frank