CELLULAR AND EMBRYONIC STUDIES ON CONGENITAL CATARACT

先天性白内障的细胞和胚胎研究

• 批准号: 3262822
• 负责人: Audray Ken Kay Harris
• 金额: $ 4.63万
• 依托单位: MEDICAL RES COUNCIL LAB OF MOLEC BIOL
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3262822
• 关键词: autosomal dominant trait; cataract; cell transformation; cellular pathology; chromosome disorders; congenital vision disorder; embryo /fetus; gene expression; genetic manipulation; genetic markers; genetic strain; histogenesis; histopathology; hybrid cells; lens proteins; mammalian embryology; mature animal; tissue /cell culture; tissue mosaicism

Congenital cataract is both an ophthalmologic and social problem. The role of hereditary has shown it forms 8.25% of all congenital cataracts. A genetic analysis in humans is not possible due to generation times and small numbers of progeny. Mouse congenital cataract mutants Cat-Fraser (Cat-Fr) and Lop provide an excellent system to study inheritance of cataract. They also provide a method to undertake in vivo and in vitro research on the growth, replication and gene expression in lenses of the cataractous mice. Breeding experiments are presently in progress to assign a specific chromosome for the dominant inherited Cat-Fr mouse. Chromosome 10 has already been mapped for the Lop cataract. Experimental chimeras formed from the aggregation of preimplantation embryos of cataractous and non-cataractous mice will attempt to "rescue" the abnormal lens defects. Blastocyst injection of cataractous cells will analyze the contribution of these cells to normal tissue. In vitro studies on clonal populations of mouse lens epithelial cells derived from Cat-Fr, Lop and normal lenses, will characterize morphological changes with replication and growth patterns, e.g. nuclear and cell size, distribution of microtubules, intermediate filaments and microfilaments, synthesis of specific lens proteins. Those in vitro parameters which are found to be associated with certan phases of the normal lens cells replication and/or growth pattern, will serve as a base line for similar studies on the lens epithelial cells derived from the cataractous mice. Somatic cell hybridization and micromanipulation techniques will be employed to study the possibility of manipulating the in vitro parameters.

先天性白内障既是眼科问题，也是社会问题。角色 遗传性白内障占所有先天性白内障的8.25%。一个 由于世代的原因，人类的基因分析是不可能的 少量的后代。小鼠先天性白内障突变体Cat-Fraser (CAT-Fr)和Lop为研究遗传提供了一个很好的系统 白内障。它们还提供了一种在体内和体外进行 大鼠晶状体生长、复制及基因表达的研究 患白内障的小鼠。育种实验目前正在进行中，分配给 显性遗传Cat-Fr小鼠的一条特殊染色体。染色体 10已经被映射为Lop白内障。实验嵌合体 由白内障和白内障植入前胚胎聚集而成 非白内障小鼠将试图“挽救”不正常的晶状体缺陷。 囊胚注射白内障细胞将分析其贡献 这些细胞转化为正常组织。银杏无性系种群的体外研究 小鼠晶状体上皮细胞来源于Cat-Fr、Lop和正常晶状体， 将通过复制和生长来表征形态变化 模式，例如核和细胞大小，微管的分布， 特殊晶状体的中间丝和微丝的合成 蛋白质。 那些被发现与Certan相关的体外参数 正常晶状体细胞复制和/或生长模式的各阶段，将 为晶状体上皮细胞的类似研究奠定了基础 来源于白内障小鼠。体细胞杂交和 微操作技术将被用来研究 操控体外参数。