BIOCHEMICAL GENETICS OF CARBONIC ANHYDRASE DEFICIENCIES

这项研究的广泛目标是继续研究遗传性 人类碳酸酐酶（CA）的缺陷，以确定 这个基因家族的不同成员的生理作用， 并确定它们的遗传相互关系。 具体目标 本项目期间有四个： 1)定义碳酸酐酶II的分子遗传学 缺陷 (CA II缺陷是新分类的基础 内分泌错误导致骨硬化症、肾小管性酸中毒和 大脑钙化。） 2)定义唾液腺分泌不足的分子遗传学 在CA II缺乏症患者中观察到的碳酸酐酶 综合征 3)描述和定义积分的相互关系 肺和肾脏中碳酸酐酶的膜形式。 4)表征表型并定义其分子基础 人的CA IV缺乏症。 这些碳酸酐酶在本实验室尚未纯化 将被纯化，表征，进行微测序， cDNA基因将被克隆和表征。 在某些情况下， 将分离指定酶的基因组DNA， 表征基因组组织，基因定位， 突变的性质改变了表达的基础， 碳酸酐酶基因

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.