V. Pringault et al., HUMAN HOMOLOGY AND CANDIDATE GENES FOR THE DOMINANT MEGACOLON LOCUS, A MOUSE MODEL OF HIRSCHSPRUNG DISEASE, Genomics, 39(1), 1997, pp. 86-89
Hirschsprung disease (HSCR) is a congenital disorder of the enteric ne
rvous system characterized by the absence of enteric ganglia. Three ge
nes for HSCR have been identified: the RET proto-oncogene, the gene co
ding for the endothelin B receptor (EDNRB), and the endothelin 3 gene
(EDN3). In mice, natural and in vitro-induced mutations affecting the
Ret, Ednrb, and Edn3 genes generate a phenotype similar to human HSCR
Another model of HSCR disease is the Dominant megacolon (Dom), a spont
aneous mouse mutation for which the target gene has not yet been ident
ified. The Dom mutation has been mapped to the middle-terminal region
of mouse chromosome 15, between D15Mit68 and D15Mit2. Using new or kno
wn polymorphisms for conserved human/mouse genes, we established the h
omology between the Dom locus and human chromosome 22q12-q13. Two gene
s, Smstr3 and Adsl, not previously mapped in the mouse genome, were lo
cated on mouse Chromosome 15. Three genes (Smstr3, Lgals1, and Pdgfb)
are possible Dom candidates, as they do not recombine with the Dom mut
ation in a 252 Dom/+ animal backcross. (C) 1997 Academic Press