Koratkar Revati, Pequignot Ed, Hauck Walter W, Siracusa Linda D
Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Cancer Res. 2002 Oct 1;62(19):5413-7.
Intestinal adenoma development in Apc(Min) mice is influenced by genetic background. We generated a congenic line between the CAST and B6 inbred strains to study the effects of a resistant CAST background in the absence of a major modifier locus, Modifier of Min 1 (Mom1(R)). Progeny from a CAST.B6 Mom1(R/S) x B6 Apc(Min/+) intercross were 110 or 200 days of age and screened for intestinal polyps. There was a significant decrease (P < 0.0001) in polyp multiplicity and size in CASTB6F1 Mom1(R/S), Apc(Min/+) and CASTB6F1 Mom1(S/S), Apc(Min/+) progeny compared with B6 Mom1(S/S), Apc(Min/+) controls. A complete absence of colon polyps was observed in all mice heterozygous for the CAST background. These results demonstrate that the CAST strain carries dominant modifier loci, in addition to Mom1(R), that dramatically reduce polyp burden in the small intestine and eliminate polyp burden in the colon of Apc(Min) mice.
Apc(Min)小鼠的肠道腺瘤发育受遗传背景影响。我们在CAST和B6近交系之间培育了一个同源系，以研究在没有主要修饰基因座Min 1修饰基因（Mom1(R)）的情况下，抗性CAST背景的影响。来自CAST.B6 Mom1(R/S)×B6 Apc(Min/+)杂交的后代在110或200日龄时接受肠道息肉筛查。与B6 Mom1(S/S)、Apc(Min/+)对照组相比，CASTB6F1 Mom1(R/S)、Apc(Min/+)和CASTB6F1 Mom1(S/S)、Apc(Min/+)后代的息肉数量和大小显著减少（P<0.0001）。在所有具有CAST背景杂合性的小鼠中均未观察到结肠息肉。这些结果表明，除Mom1(R)外，CAST品系携带显性修饰基因座，可显著减轻Apc(Min)小鼠小肠中的息肉负担，并消除结肠中的息肉负担。
