CLONING AND CHARACTERIZATION OF A MOUSE GENE WITH HOMOLOGY TO THE HUMAN VON HIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE - IMPLICATIONS FOR THE POTENTIAL ORGANIZATION OF THE HUMAN VON HIPPEL-LINDAU DISEASE GENE

The human von Hippel-Lindau disease (VHL) gene has recently been ident ified and, based on the nucleotide sequence of a partial cDNA clone, h as been predicted to encode a novel protein with as yet unknown functi ons [F. Latif et at, Science (Washington DC), 260: 1317-1320, 1993]. T he length of the encoded protein and the characteristics of the cellul ar expressed protein are as yet unclear. Here we report the cloning an d characterization of a mouse gene (mVHLh1) that is widely expressed i n different mouse tissues and shares high homology with the human VHL gene. It predicts a protein 181 residues long (and/or 162 amino acids, considering a potential alternative start codon), which across a core region of similar to 140 residues displays a high degree of sequence identity (98%) to the predicted human VHL protein. High stringency DNA and RNA hybridization experiments and protein expression analyses ind icate that this gene is the most highly VHL-related mouse gene, sugges ting that it represents the mouse VHL gene homologue rather than a rel ated gene sharing a conserved functional domain. These findings provid e new insights into the potential organization of the VHL gene and nat ure of its encoded protein.