Agrin promotes anophthalmia and microphthalmia

描述（由申请方提供）：无眼症和小眼症是在C57 BL/6 J小鼠中自发发生的眼睛发育缺陷，发生频率为1%至12%。最近产生的几种C57 BL/6 J小鼠品系具有增加的这些缺陷的发生率，包括其中一个品系，其突变是完全的，但取决于遗传背景。这些小鼠携带与CFP融合的聚集蛋白转基因的多个拷贝。聚集蛋白在神经肌肉接头的发育中起关键作用。聚集蛋白也在视网膜和玻璃体血管中表达，尽管其在这些组织中的功能尚不清楚。该项目的第一个目标是表征聚集蛋白CFP在发育中的眼睛中的表达，以及对各种发育缺陷的类型和起始进行编目。该项目的第二个目标是利用C57 BL/6 J小鼠中这些表型的增加的突变率来绘制无眼症和小眼症的修饰符。这项工作将增加对眼睛如何发育以及agrin在这一过程中所起作用的理解。

DESCRIPTION (provided by applicant):Anophthalmia and microphthalmia are defects in the development of the eye occurring spontaneously at a frequency of one to twelve percent in C57BL/6J mice. Several recently generated strains of C57BL/6J mice have an increased incidence of these defects including one line in which penetrance is complete, but dependent on the genetic background. These mice carry multiple copies of an agrin transgene fused to CFP. Agrin plays a critical role in development of the neuromuscular junction. Agrin is also expressed in the retina and hyaloid vessels although its function in these tissues is unknown. The first goal of this project is to characterize the expression of agrin-CFP in the developing eye as well as cataloging the types and initiation of various developmental defects. The second goal of this project, to map modifiers of anophthalmia and microphthalmia, takes advantage of the increased penetrance of these phenotypes in C57BL/6J mice. This work will increase understanding of how the eye develops and the role agrin plays in this process.