MUCOPOLYSACCHARIDOSIS TYPE-VI IN RATS - ISOLATION OF CDNAS ENCODING ARYLSULFATASE-B, CHROMOSOMAL LOCALIZATION OF THE GENE, AND IDENTIFICATION OF THE MUTATION

Mucopolysaccharidosis (MPS) type VI, the lysosomal storage disorder ca used by the deficiency of arylsulfatase B (ARSB) activity, occurs in h umans, cats, and rats. To characterize the molecular lesion(s) causing MPS VI in rats, cDNAs encoding rat ARSB were isolated from a rat live r cDNA library, The nucleotide and deduced amino acid sequences of rat ARSB had similar to 80 and 85% identity with the human ARSB sequences , respectively. The chromosomal location of the rat ARSB gene was dete rmined by PCR analysis of rat-mouse somatic cell hybrid panel. The ARS B gene was assigned to rat chromosome 2, where the locus for the MPS V t phenotype in rats has been localized by linkage analysis. To identif y the mutation(s) within the ARSB gene causing MPS VI in rats, the ARS B sequence were amplified from affected animals and completely sequenc ed. Notably, a homoallelic one-base insertion at nucleotide 507 (507in sC) was identified, resulting in a frame shift mutation and premature termination at codon 258. The presence of the insertion completely cor related with the occurrence of the MPS VI phenotype among 66 members o f 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 mo del of human MPS VI. (C) 1995 Academic Press, Inc.