BIOCHEMICAL GENETICS OF CARBONIC ANHYDRASE DEFICIENCIES

这项研究的总体目标是继续研究遗传的 人碳酸酐酶(CA)的缺陷以确定 这个基因家族中不同成员的生理作用， 并确定它们之间的遗传相互关系。具体目标 在本项目期内有四个项目： 1)定义碳酸酐酶II的分子遗传学 缺乏症。(CA II缺乏症是新分类的基础 出生错误导致骨质疏松症、肾小管酸中毒和 大脑钙化。) 2)界定唾液虚证的分子遗传学 CA II缺乏症患者的碳酸氢酶 综合症。 3)刻画和定义积分的相互关系 肺和肾中碳酸酐酶的膜形态。 4)表征表型并确定其分子基础 人类CA IV缺乏症。 我们实验室尚未提纯的那些碳酸酐酶 将被提纯、鉴定、进行显微测序，以及 这些基因将被克隆和鉴定。在某些情况下， 指定酶的基因组DNA将被分离出来 描述基因组组织、基因定位和 导致基因表达改变的突变的性质 碳酸氢酶基因。

The broad goal of this research is to continue studies of inherited deficiencies of human carbonic anhydrases (CAs) in order to define the physiologic roles of the various members of this gene family, and to define their genetic interrelationships. The specific aims for this project period are four: 1) Define the molecular genetics of carbonic anhydrase II deficiency. (CA II deficiency is the basis for a newly classified inbor error producing osteopetrosis, renal tubular acidosis and cerebral calcification.) 2) Define the molecular genetics of the deficiency of salivary carbonic anhydrase which is seen in patients with CA II deficiency syndrome. 3) Characterize and define the interrelationships of the integral membrane forms of carbonic anhydrase in lung and kidney. 4) Characterize the phenotype and define the molecular basis of CA IV deficiency in man. Those carbonic anhydrases no already purified in our laboratory will be purified, characterized, subjected to microsequencing, and the cDNA genes will be cloned and characterized. In some cases, the genomic DNA specifying the enzymes will be isolated to characterize the genomic organization, gene localization, and the nature of the mutation underlying the altered expression of the carbonic anhydrase gene.