Koratkar Revati, Silverman Karen A, Pequignot Ed, Hauck Walter W, Buchberg Arthur M, Siracusa Linda D
Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107, USA.
Genomics. 2004 Nov;84(5):844-52. doi: 10.1016/j.ygeno.2004.07.010.
Genetic background affects polyp development in the Multiple intestinal neoplasia (Apc(Min)) mouse model. The Modifier of Min 1 (Mom1) locus accounts for approximately 50% of the variation in polyp multiplicity. We generated reciprocal congenic lines, such that the recipient C57BL/6J (B6) strain carries a donor C3H/HeJ (C3H) Mom1 allele, and the recipient C3H strain carries a donor B6 Mom1 allele. Hybrid progeny from congenic females mated to B6 Apc(Min/+) males were analyzed. A single C3H Mom1 locus on the B6 background reduced small intestinal polyp numbers by 50% and colon polyp incidence by 66% compared to their susceptible B6 Mom1(S/S)Apc(Min/+) siblings. These findings show that the C3H genome contains a resistant Mom1(R) locus. The reciprocal congenic line, which carries the susceptible B6 Mom1(S) locus on the C3H background, reduced small intestinal polyp numbers by 80% and colon polyp incidence by 95% compared to B6 Mom1(S/S)Apc(Min/+) mice. These data demonstrate that unidentified modifiers in the C3H strain can suppress intestinal polyp multiplicity in Apc(Min/+) mice, and act in the absence of a resistant Mom1(R) locus.
遗传背景影响多发性肠肿瘤（Apc(Min)）小鼠模型中的息肉发育。Min 1修饰基因（Mom1）位点约占息肉多发性变异的50%。我们构建了 reciprocal congenic 品系，使受体C57BL/6J（B6）品系携带供体C3H/HeJ（C3H）的Mom1等位基因，而受体C3H品系携带供体B6的Mom1等位基因。分析了将 congenic 雌性小鼠与B6 Apc(Min/+)雄性小鼠杂交产生的后代。与易患的B6 Mom1(S/S)Apc(Min/+)同胞相比，B6背景上的单个C3H Mom1位点使小肠息肉数量减少了50%，结肠息肉发生率降低了66%。这些发现表明C3H基因组包含一个抗性Mom1(R)位点。在C3H背景上携带易感性B6 Mom1(S)位点的 reciprocal congenic 品系，与B6 Mom1(S/S)Apc(Min/+)小鼠相比，小肠息肉数量减少了80%，结肠息肉发生率降低了95%。这些数据表明，C3H品系中未鉴定的修饰基因可以抑制Apc(Min/+)小鼠的肠道息肉多发性，并且在没有抗性Mom1(R)位点的情况下起作用。 （注：“reciprocal congenic”直译为“相互同源基因的”，这里保留英文是因为不确定在该专业领域是否有更准确的中文术语）
