New Mouse Models of Microphthamia

新的小口症小鼠模型

基本信息

批准号：
7296420
负责人：
EDWARD M LEVINE
金额：
$ 14.95万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2009-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Congenital eye defects are relatively common and oftentimes impair vision or cause blindness. Microphthalmia is a severe congenital eye defect in which the eye fails to grow to its normal size, among other problems. Because the onset of microphthalmia occurs early in fetal development, very little is known about its primary causes or the changes that occur in human eye development. In the past few years, several genes have been conclusively linked to microphthalmia in humans. One of them, Chx10, causes non-syndromic, bilateral microphthalmia and children with this condition are born blind. Three missense mutations have been identified, but the progression of ocular development in humans with these mutations is not known. The primary goal of these studies is to characterize the developmental phenotypes caused by the mutations in Chx10 that are founding humans. Our approach is to produce two of the three human mutations in the mouse using transgenic knock-in technology and characterize the resulting phenotypes. Phenotypes will be determined in embryos, neonates, and adult mice by histological methods including in situ hybridization and immunohistochemistry. Completion of these studies could provide significant insight into the developmental changes associated with microphthalmia in humans and further resolve the role of Chx10 in eye formation, and in particular, retinal development. Congenital eye anomalies are relatively common birth defects that cause visual impairments or blindness. Microphthalmia, or small eye, is a severe anomaly for which there is no available corrective treatment. Three mutations in the Chx10 gene cause micropthalmia in humans. We have generated mouse models that carry two of the human mutations and an important goal of this grant is to characterize the defects that occur during eye development in order to better understand the etiology of human microphthalmia.

描述（由申请人提供）：先天性眼部缺陷相对常见，通常会损害视力或导致失明。小眼症是一种严重的先天性眼部缺陷，其中包括眼睛无法生长到正常大小等问题。由于小眼球的发病发生在胎儿发育早期，因此对其主要原因或人眼发育中发生的变化知之甚少。在过去的几年中，一些基因已被确定与人类小眼症相关。其中一种 Chx10 会导致非综合征性双侧小眼球，患有这种疾病的儿童生来就失明。已鉴定出三种错义突变，但携带这些突变的人类眼部发育进展尚不清楚。这些研究的主要目标是表征由人类创始者 Chx10 突变引起的发育表型。我们的方法是使用转基因敲入技术在小鼠中产生三种人类突变中的两种，并表征所得的表型。将通过原位杂交和免疫组织化学等组织学方法确定胚胎、新生儿和成年小鼠的表型。这些研究的完成可以为人类小眼症相关的发育变化提供重要的见解，并进一步解决 Chx10 在眼睛形成，特别是视网膜发育中的作用。先天性眼睛异常是相对常见的出生缺陷，会导致视力障碍或失明。小眼症或小眼睛是一种严重的异常现象，目前尚无可用的纠正治疗方法。 Chx10 基因的三种突变会导致人类小眼症。我们已经生成了携带两种人类突变的小鼠模型，这笔资助的一个重要目标是描述眼睛发育过程中发生的缺陷的特征，以便更好地了解人类小眼症的病因学。