Hagan John P, Kozlov Serguei V, Chiang Yisheng, Sewell Lori, Stewart Colin L
Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-FCRDC, National Institutes of Health, P.O. Box B, Frederick, MD 21702, USA.
Genomics. 2004 Nov;84(5):836-43. doi: 10.1016/j.ygeno.2004.07.007.
Maternal inheritance of targeted loss of function alleles encoding either the cyclin-dependent kinase inhibitor 1C (Cdkn1c) or the insulin-like growth factor 2 receptor (Igf2r) leads to fully penetrant perinatal lethality in C57BL/6J mice due to genomic imprinting. Here, we demonstrate that there is a marked enhancement in postnatal viability of F(1) mice carrying either the ablated Igf2r ( approximately 32%) or Cdkn1c ( approximately 83%) when the paternal genome was derived from the inbred Mus musculus musculus CzechII/Ei strain. Genetic and molecular analyses indicated that the increased viability was not caused by relaxation of imprinted gene expression, but is the consequence of unidentified polygenic modifiers that are not imprinted. In the course of this study, restriction-site polymorphisms between 129S1 and CzechII/Ei in 21 imprinted and 14 biallelically expressed genes were identified. These polymorphisms may prove useful in determining the effects of different mutant backgrounds on genomic imprinting.
由于基因组印记，编码细胞周期蛋白依赖性激酶抑制剂1C（Cdkn1c）或胰岛素样生长因子2受体（Igf2r）的功能缺失等位基因的母系遗传会导致C57BL/6J小鼠出现完全显性的围产期致死率。在此，我们证明，当父本基因组来自近交系小家鼠捷克II/Ei品系时，携带缺失的Igf2r（约32%）或Cdkn1c（约83%）的F(1)小鼠的出生后存活率有显著提高。遗传和分子分析表明，存活率的提高不是由印记基因表达的放松引起的，而是由未印记的未知多基因修饰因子导致的。在本研究过程中，鉴定了21个印记基因和14个双等位基因表达基因中129S1和捷克II/Ei之间的限制性位点多态性。这些多态性可能有助于确定不同突变背景对基因组印记的影响。
