MURINE ALPHA-L-IDURONIDASE - CDNA ISOLATION AND EXPRESSION

As an initial step toward the generation of a murine model for mucopolysaccharidosis type I, we have identified and characterized a full-length murine alpha-L-iduronidase cDNA. Expression of the murine cDNA in COS-1 cells results in the production of alpha-L-iduronidase enzyme activity at a level 20-fold higher than that of the endogenous gene. The murine cDNA shows strong homology with the coding region of both the human and the canine homologs with 78 and 75% nucleotide sequence identity, respectively. In contrast to the coding region, significant diversity of sequence exists for the 5' and 3' untranslated regions between the murine and both the human and the canine sequence. The 3' UTR of the murine transcript is 1193 bp in length, as compared to the human (100 bp) and canine (139 bp), and contains a CA dinucleotide repeat not seen in either the human or the canine genes. A portion of the murine iduronidase coding sequence overlaps with sequence reported for the 3' UTR of the murine SAT-1 cDNA. The sequence overlap involves the proposed exon II of murine iduronidase and covers 141 bp of sequence with the transcripts generated in opposite orientation. We report here the characterization of murine alpha-L-iduronidase cDNA and its relationship to SAT-1. (C) 1994 Academic Press, Inc.