Kunieda T, Simonaro C M, Yoshida M, Ikadai H, Levan G, Desnick R J, Schuchman E H
Department of Human Genetics, Mount Sinai School of Medicine, New York, New York, USA.
Genomics. 1995 Oct 10;29(3):582-7. doi: 10.1006/geno.1995.9962.
Mucopolysaccharidosis (MPS) type VI, the lysosomal storage disorder caused by the deficiency of arylsulfatase B (ARSB) activity, occurs in humans, cats, and rats. To characterize the molecular lesion(s) causing MPS VI in rats, cDNAs encoding rat ARSB were isolated from a rat liver cDNA library. The nucleotide and deduced amino acid sequences of rat ARSB had approximately 80 and 85% identity with the human ARSB sequences, respectively. The chromosomal location of the rat ARSB gene was determined by PCR analysis of rat-mouse somatic cell hybrid panel. The ARSB gene was assigned to rat chromosome 2, where the locus for the MPS VI phenotype in rats has been localized by linkage analysis. To identify the mutation(s) within the ARSB gene causing MPS VI in rats, the ARSB sequence were amplified from affected animals and completely sequenced. Notably, a homoallelic one-base insertion at nucleotide 507 (507insC) was identified, resulting in a frame shift mutation and premature termination at codon 258. The presence of the insertion completely correlated with the occurrence of the MPS VI phenotype among 66 members of the MPR rat colony. Thus, we conclude that 507insC is the causative mutation in these animals and that the MPS VI rats are an authentic model of human MPS VI.
VI型黏多糖贮积症（MPS）是一种由芳基硫酸酯酶B（ARSB）活性缺乏引起的溶酶体贮积症，可发生于人类、猫和大鼠。为了确定导致大鼠MPS VI的分子损伤，从大鼠肝脏cDNA文库中分离出编码大鼠ARSB的cDNA。大鼠ARSB的核苷酸序列和推导的氨基酸序列与人类ARSB序列的同源性分别约为80%和85%。通过对大鼠-小鼠体细胞杂交板进行PCR分析，确定了大鼠ARSB基因的染色体定位。ARSB基因被定位到大鼠的2号染色体上，通过连锁分析已将大鼠MPS VI表型的基因座定位在此处。为了鉴定导致大鼠MPS VI的ARSB基因内的突变，从患病动物中扩增出ARSB序列并进行了全序列测定。值得注意的是，在核苷酸507处发现了一个纯合的单碱基插入（507insC），导致移码突变并在第258密码子处提前终止。在MPR大鼠群体的66个成员中，该插入的存在与MPS VI表型的出现完全相关。因此，我们得出结论，507insC是这些动物中的致病突变，并且MPS VI大鼠是人类MPS VI的真实模型。
