THE HYALURONIDASE GENE HYAL1 MAPS TO CHROMOSOME 3P21.2-P21.3 IN HUMANAND 9F1-F2 IN MOUSE, A CONSERVED CANDIDATE TUMOR-SUPPRESSOR LOCUS

We recently cloned and expressed the major hyaluronidase activity from human plasma, HYAL1, and found that the protein is 40% identical to t he testicular hyaluronidase, PH-20. The HYAL1 mRNA sequence was used i n a homology search of the mouse database of expressed sequence tags ( dbEST). Two ESTs were obtained and, in combination with 5'RACE-PCR, we re used to clone the mouse HYAL1 ortholog (Hyal1). Hyal1 codes for a p rotein of 462 amino acids that is 73% identical to the human sequence. Hyal1 stably expressed in human embryonic kidney cells resulted in a 20,000 fold increase of hyaluronidase activity. Sequence-tagged sites derived from the HYAL1 gene from both species were used to isolate P1 genomic clones that were used as probes for fluorescence in situ hybri dization. The human gene was localized to chromosome 3p21 and the mous e gene to a syntenic region on chromosome 9F1-F2. In mouse, serum hyal uronidase polymorphism has previously been mapped by an interspecific backcross to 60 cM from the centromere of chromosome 9, which correspo nds to a cytogenetic location of 9F1-F2. The mouse Hyal1 gene is there fore very Likely to be responsible for the hyaluronidase polymorphism linked to this locus. We also present evidence that human HYAL1 is ide ntical to an uncharacterized gene positionally cloned by others from c hromosome 3p21.3 that is homozygously deleted in several small-cell lu ng carcinoma cell lines. (C) 1998 Academic Press.