Cloning and partial sequencing of beta-glucuronidase

, one of the anchor loci type I, in the dog. Homology with human, mouse, rat and E. coli sequences.

A BOUVET, M E HASKINS, J H WOLFE, D F PATTERSON & P S HENTHORN.

Pathology and Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Mucopolysaccharidosis type VII (MPS VII) is an inherited disease resulting from the deficiency in activity of the lysosomal hydrolase enzyme beta-glucuronidase (GUSB), reported in humans, mice, cats and dogs.

As a first step toward the elucidation of the molecular basis of this disease in dogs, we have screened a canine testis cDNA library. Our clones isolated to date contain 2.0 kb of the full-length 2.2 kb cDNA. The sequences have been determined and compared with published human, mouse,rat and E. coli GUSB DNA sequences. The GUSB gene has been well conserved throughout evolution (49% identity between dog and E. coli sequences) and the dog cDNA sequence is more closely related to the human cDNA sequence (80%) than to mouse or rat cDNAs (77 and 76%, respectively). The coding sequences of dog and human GUSB contain three more amino acids than rat and mouse in one contiguous segment, and two of those amino acids are identical in man and dog. Three potential N-glycosylation sites are present at the same location in all mammalian species as are three cysteine residues. The 3 ' untranslated region (3' UNT) of the dog GUSB cDNA contains 170 bp from the TGA stop codon to the poly A tail and has 62% homology with the 210 bp of the 3' UNT region in human GUSB cDNA. No homology has been found with the rodents 3' UNT region.

Overall, the dog cDNA sequence is closer to that of human GUSB than that of rodents. GUSB has been designated anchor locus type I for Comparative Gene Mapping and its use will aid in extending the canine gene map.


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