Isolation and Characterization of Thiamin-Responsive Megaloblastic Anemia Gene

硫胺素反应性巨幼细胞性贫血(TRMA；OMIM 249270)是一种常染色体隐性遗传病，表现为对硫胺素治疗有反应的巨幼细胞性贫血、糖尿病和感觉神经性耳聋。尽管TRMA的病理生理机制尚不清楚，该综合征的基因也尚未确定，但硫胺素焦磷酸激酶(TPK)或硫胺素转运系统极有可能是这种异常蛋白的候选蛋白。我们已经从酿酒酵母中分离到了TPK基因THI80和一株突变株THI80。随后，我们尝试以酵母Thi80菌株为宿主细胞，通过功能互补的方法分离人TPK基因，但未能获得克隆。现在，我们开始与科恩博士(以色列理工学院)一起使用位置克隆策略来定位TRMA基因。另一方面，我们从酿酒酵母和一株thi10突变株中克隆了硫胺素转运蛋白基因THI10。利用这些材料，我们将尝试克隆人类硫胺素运输蛋白的cDNAs。

Thiamin-responsive megaloblastic anemia (TRMA ; OMIM 249270) is an autosomal recessive disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus, and sensorineural deafness, responding to thiamin treatment. Although the pathophysiology of TRMA remains obscure and the gene for the syndrome has not been identified yet, it is highly possible that thiamin pyrophosphokinase (TPK) or thiamin transport system is a candidate for the aberrant protein. We have already isolated a TPK gene, THI80, from yeast Saccharomyces cerevisiae and also a thi80 mutant strain. Then we tried to isolate the human TPK cDNA by the functional complementation using yeast thi80 strain as the host cell, but we have not obtained the clone. Now we started to map the TRMA gene using positional cloning strategy with Dr.Cohen (Technion-Israel Institute of Technology). On the other hand, we cloned the gene encoding thiamin transport protein, THI10, from S.cerevisiae and a thi10 mutant strain. Using these materials, we are going to try the cloning of the human cDNA of the thiamin transport protein.