Somatic Reactivation of Expression of the Silent Maternal Mest Allele and Acquisition of Normal Reproductive Behaviour in a Colony of Peg1/Mest Mutant Mice
Somatic Reactivation of Expression of the Silent Maternal Mest Allele and Acquisition of Normal Reproductive Behaviour in a Colony of Peg1/Mest Mutant Mice
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DOI：
10.1262/jrd.11-115a
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发表时间：
2012-08-01
影响因子：
1.8
通讯作者：
Eccles, Michael R.
中科院分区：
文献类型：
--
作者：
Ineson, Jessica;Stayner, Cherie;Eccles, Michael R.
基因组印迹在不到1%的基因中以亲本特有的方式赋予等位基因特异性表达。在人类和小鼠中，Peg1/Mest基因(Mest)在母系中受到抑制，在父系中表达。Mest在胚胎发育的中胚层组织和成人脑中表达，父系突变会导致发育迟缓和母体行为缺陷。尽管我们目前对Mest和其他印记基因印记的建立机制有所了解，但尚不清楚Mest印记需要在多大程度上保持在成人组织中。已知印迹异常发生在某些罕见的综合征中，涉及遗传性突变或受精后不久发生的结构性表观遗传学改变。成年个体衰老的体细胞组织中也可能出现印迹异常。在这里，我们报告了在一群小鼠中发生了胚胎后Mest等位基因表达的体细胞变异，其中从父亲继承的Mest突变印记基因座的杂合子自发表达了来自母亲的正常沉默的等位基因。此外，新获得的克服母体生殖行为缺陷的能力发生在突变小鼠身上，但这似乎与Mest突变没有直接联系。我们的结果表明，在成年个体的体细胞组织中至少需要一个Mest表达的等位基因，在某些条件下(如Mest插入突变的存在或在遗传背景改变的情况下)，Mest基因座上的等位基因表达可能发生躯体获得性改变。
Genomic imprinting confers allele-specific expression in less than 1% of genes, in a parent-of-origin specific fashion. In humans and mice the Peg1/Mest gene (Mest) is maternally repressed, and paternally expressed. Mest is expressed in embryogenic mesoderm-derived tissues and in adult brain, and paternal mutations in Mest lead to growth retardation and defective maternal behaviour. Despite our current understanding of mechanisms associated with the establishment of imprinting of Mest and other imprinted genes, it is unclear to what extent Mest imprinting needs to be maintained in adult tissues. Aberrations of imprinting are known to occur in certain rare syndromes, and involve either inherited mutations, or constitutive epigenetic alterations occurring soon after fertilization. Imprinting abnormalities may also occur in the aging somatic tissues of adult individuals. Here we report an occurrence of post-embryonic somatic variability of Mest allelic expression in a colony of mice where heterozygotes at the imprinted Mest locus for a mutation inherited from the father spontaneously expressed the normally silenced allele from the mother. In addition, a newly acquired ability to overcome the deficit in maternal reproductive behaviour had occurred in the mutant mice, but this appeared not to be directly linked to the Mest mutation. Our results suggest that at least one allele of Mest expression is required in the somatic tissues of adult individuals and that under certain conditions (such as in the presence of a Mest insertional mutation or in an altered genetic background), somatically acquired alterations of allelic expression at the Mest locus may occur.