Analysis of mouse conceptuses with uniparental duplication/deficiency for distal chromosome 12: comparison with chromosome 12 uniparental disomy and implications for genomic imprinting
Analysis of mouse conceptuses with uniparental duplication/deficiency for distal chromosome 12: comparison with chromosome 12 uniparental disomy and implications for genomic imprinting
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DOI：
10.1159/000090835
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发表时间：
2006-01-01
影响因子：
1.7
通讯作者：
Ferguson-Smith, A. C.
中科院分区：
文献类型：
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作者：
Tevendale, M.;Watkins, M.;Ferguson-Smith, A. C.
小鼠 12 号染色体远端有印迹。对整个 12 号染色体具有母本或父本单亲二倍体的小鼠胚胎进行表型分析，表征了与该染色体上印记基因剂量改变相关的发育缺陷。在这里，我们使用相互易位 T(4; 12)47H 对母本和父本 Dp(dist12) 小鼠进行表征。这将分析区域限制在小鼠 12 号染色体上 B3 中 T47H 断点远端的染色体域。MatDp(dist12)T47H 和 PatDp(dist12)T47H 受孕者均无法存活，并且在交配后 10.5 天 (dpc) 时 Dp(dist12) 受孕者的恢复频率低于正常相邻 1 分离后的预期。 MatDp(dist12) 胚胎的一个子集可以在产后存活一天。与父本单亲二倍体 12 胚胎相比，妊娠 16.5 天后没有回收到活的 PatDp (dist12) 胚胎。在母本和父本 12 号染色体单亲二倍体小鼠中观察到的其他表型在 Dp(dist12) 小鼠中得到重现，包括胎盘、肌肉和骨骼缺陷。 MatDp(dist12) 和母体单亲二倍体 12 胚胎的皮肤中还发现了其他缺陷。这项研究表明，与小鼠 12 号染色体起源改变相关的发育异常可归因于 T47H 断点远端的基因组区域。
Distal mouse chromosome 12 is imprinted. Phenotypic analysis of mouse embryos, with maternal or paternal uniparental disomy for the whole of chromosome 12 has characterized the developmental defects associated with the altered dosage of imprinted genes on this chromosome. Here we conduct a characterization of maternal and paternal Dp(dist12) mice using the reciprocal translocation T(4; 12)47H. This limits the region analysed to the chromosomal domain distal to the T47H breakpoint in B3 on mouse chromosome 12. Both MatDp(dist12)T47H and PatDp(dist12)T47H conceptuses are non-viable and the frequency of recovery of Dp(dist12) conceptuses by 10.5 days post coitum (dpc) was lower than expected after normal adjacent-1 disjunction. A subset of MatDp(dist12) embryos can survive up to one day post partum. In contrast to paternal uniparental disomy 12 embryos, no live PatDp (dist12) embryos were recovered after 16.5 days of gestation. Other phenotypes observed in maternal and paternal chromosome 12 uniparental disomy mice are recapitulated in the Dp(dist12) mice and include placental, muscle and skeletal defects. Additional defects were also noted in the skin of both MatDp(dist12) and maternal uniparental disomy 12 embryos. This study shows that the developmental abnormalities associated with the altered parent of origin for mouse chromosome 12 can be attributed to the genomic region distal to the T47H breakpoint.