Aspartoacylase gene, protein, and methods of screening for mutations associated with Canavan disease
申请人:Miami Children's Hospital Research Inst.
公开号:US20030017473A1
公开(公告)日:2003-01-23
Canavan disease, an autosomal recessive leukodystrophy, is caused by deficiency of aspartoacylase and accumulation of N-acetylaspartic acid in brain. Human aspartoacylase (ASP) cDNA spanning 1,435 bp has been cloned and expressed in
E. coli.
A base change, a854>c, has been found in 85% of the 34 Canavan alleles tested so far, which results in a missense glu285>ala mutation that is predicted to be part of the catalytic domain of aspartoacylase. The invention therefore provides nucleic acid sequences, genes, polypeptides, antibodies, vectors containing the gene, host cells transformed with vectors containing the gene, animal models for the disease, methods for expressing the polypeptide, genetic screening methods and kits, diagnostic methods and kits, methods of treating Canavan disease and methods of genetic therapy for the disease.
Canavan病是一种常染色体隐性遗传的白质脑病,由于天冬氨酸乙酰化酶的缺乏和N-乙酰天冬氨酸在大脑中的积累而引起。人类天冬氨酸乙酰化酶(ASP)cDNA跨越1435个碱基被克隆并在大肠杆菌中表达。迄今已经测试了34个Canavan等位基因中的85%,发现一个a854>c的碱基变化,导致一个预测为天冬氨酸乙酰化酶催化结构域的错义glu285>ala突变。因此,本发明提供了核酸序列、基因、多肽、抗体、含有该基因的载体、转化有该基因载体的宿主细胞、用于该疾病的动物模型、表达多肽的方法、遗传筛查方法和试剂盒、诊断方法和试剂盒、治疗Canavan病的方法以及该疾病的基因治疗方法。