Pingault V, Puliti A, Préhu M O, Samadi A, Bondurand N, Goossens M
INSERM U91, Hôpital Henri Mondor, Créteil, France.
Genomics. 1997 Jan 1;39(1):86-9. doi: 10.1006/geno.1996.4476.
Hirschsprung disease (HSCR) is a congenital disorder of the enteric nervous system characterized by the absence of enteric ganglia. Three genes for HSCR have been identified: the RET proto-oncogene, the gene coding 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 spontaneous mouse mutation for which the target gene has not yet been identified. The Dom mutation has been mapped to the middle-terminal region of mouse chromosome 15, between D15Mit68 and D15Mit2. Using new or known polymorphisms for conserved human/mouse genes, we established the homology between the Dom locus and human chromosome 22q12-q13. Two genes, Smstr3 and Adsl, not previously mapped in the mouse genome, were located on mouse Chromosome 15. Three genes (Smstr3, Lgals1, and Pdgfb) are possible Dom candidates, as they do not recombine with the Dom mutation in a 252 Dom/+ animal backcross.
先天性巨结肠症（HSCR）是一种以肠神经节缺失为特征的先天性肠道神经系统疾病。已鉴定出三个与HSCR相关的基因：RET原癌基因、内皮素B受体（EDNRB）编码基因和内皮素3基因（EDN3）。在小鼠中，影响Ret、Ednrb和Edn3基因的自然突变和体外诱导突变会产生与人类HSCR相似的表型。HSCR疾病的另一个模型是显性巨结肠（Dom），这是一种自发的小鼠突变，其靶基因尚未确定。Dom突变已定位到小鼠15号染色体的中末端区域，位于D15Mit68和D15Mit2之间。利用保守的人类/小鼠基因的新多态性或已知多态性，我们确定了Dom基因座与人类22号染色体q12-q13之间的同源性。两个以前未在小鼠基因组中定位的基因Smstr3和Adsl位于小鼠15号染色体上。三个基因（Smstr3、Lgals1和Pdgfb）可能是Dom的候选基因，因为在252只Dom/+动物回交中它们不与Dom突变重组。
