McLaughlin K J, Szabó P, Haegel H, Mann J R
Division of Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
Development. 1996 Jan;122(1):265-70. doi: 10.1242/dev.122.1.265.
Imprinted genomic regions have been defined by the production of mice with uniparental inheritance or duplication of homologous chromosome regions. With most of the genome investigated, paternal duplication of only distal chromosomes 7 and 12 results in the lack of offspring, and prenatal lethality is presumed. Aberrant expression of imprinted genes in these two autosomal regions is therefore strongly implicated in the periimplantation lethality of androgenetic embryos. We report that mouse embryos with paternal duplication of distal chromosome 7 (PatDup.d7) die at midgestation and lack placental spongiotrophoblast. Thus, the much earlier death of androgenones must involve paternal duplication of other autosomal regions, acting independently of or synergistically with PatDup.d7. The phenotype observed is similar, if not identical to, that resulting from mutation of the imprinted distal chromosome 7 gene, Mash2, which in normal midgestation embryos exhibits spongiotrophoblast-specific maternally active/paternally inactive (m+/p-) allelic expression. Thus, the simplest explanation for the PatDup.d7 phenotype is p-/p- expression of this gene. We also confirm that PatDup.d7 embryos lack H19 RNA and posses excess Igf2 RNA as might be expected from the parental-specific activities of these genes in normal embryos.
印记基因组区域是通过产生具有单亲遗传或同源染色体区域重复的小鼠来定义的。在对大部分基因组进行研究后发现，仅父本来源的远端7号和12号染色体重复会导致没有后代，推测存在产前致死性。因此，这两个常染色体区域中印迹基因的异常表达与孤雄生殖胚胎在着床前期的致死性密切相关。我们报告称，父本来源的远端7号染色体重复（PatDup.d7）的小鼠胚胎在妊娠中期死亡，且缺乏胎盘海绵滋养层细胞。因此，孤雄生殖胚胎更早的死亡必定涉及其他常染色体区域的父本重复，其独立于PatDup.d7或与之协同作用。观察到的表型即便不完全相同，也与印记远端7号染色体基因Mash2突变所导致的表型相似，在正常妊娠中期胚胎中，该基因表现出海绵滋养层细胞特异性的母本活跃/父本沉默（m+/p-）等位基因表达。因此，对PatDup.d7表型最简单的解释是该基因的p-/p-表达。我们还证实，PatDup.d7胚胎缺乏H19 RNA，并且拥有过量的Igf2 RNA，这与这些基因在正常胚胎中的亲本特异性活性预期一致。
