ASSIGNMENT OF MOUSE GFRA1, THE HOMOLOG OF A NEW HUMAN HSCR CANDIDATE GENE, TO THE TELOMERIC REGION OF MOUSE-CHROMOSOME-19

Glial cell line-derived neurotrophic factor (Gdnf) and its alpha recep tor (Gfra1) interact with the Ret receptor triggering its tyrosine kin ase activity. As Gdnf and Ret have been linked to the development of H irschsprung disease (HSCR), it seems likely that Gfra1 could also be a susceptibility gene for HSCR. A further HSCR candidate gene is repres ented by the human homologue of the Dom (Dominant megacolon) mouse mut ation, mapped to Chr 15, for which the gene has not yet been identifie d. In order to test if Gfra1 could be the Dom gene or if it represents a new possible HSCR locus we have undertaken the mapping of the mouse Gfra1. Using specific PCR primers on a somatic cell hybrid mapping pa nel and fluorescence in situ hybridization with an expressed sequence tag (EST) cDNA clone corresponding to the mouse Gfra1, we mapped the g ene to mouse chromosome 19D2-D3, a region with known homology with hum an chromosome 10q24-->q26.