Department of Biomedical Sciences, University of Missouri, Christopher S. Bond Life Sciences Center, 1201 East Rollins Rd., Columbia, MO 65211, USA.
Biol Reprod. 2010 Mar;82(3):473-88. doi: 10.1095/biolreprod.109.080952. Epub 2009 Oct 14.
Epigenetics provides a means of understanding how environmental factors might alter heritable changes in gene expression without changing DNA sequence, and hence the origin, of some diseases that are not explained by conventional genetic mechanisms. Various animal models have been described, most notably the agouti viable yellow (A(vy)) and axin 1 fused (Axin1(Fu)) mice, which lend themselves particularly well to studying this link between epigenetics and development abnormalities, because particular changes in DNA methylation patterns can be linked to a broad spectrum of heritable pathologies in the mice. In addition, there are specific examples, both in mice and other animal species, where nonmutagenic, environmental insults to either parent, such as those caused by consumption of endocrine-disrupting chemicals, can cause unexpected transgenerational phenotypic changes in offspring. Animals derived by somatic cell nuclear transfer also frequently exhibit pathologies that can be linked to inappropriate nuclear reprogramming during early embryo development and provide another means to study a link between epigenetics and disease. This review will consider how all of these animal models might help elucidate the epigenetic basis for a wide range of phenotypes.
表观遗传学提供了一种理解环境因素如何在不改变 DNA 序列的情况下改变基因表达的可遗传变化的方法，从而解释了一些不能用传统遗传机制解释的疾病的起源。已经描述了各种动物模型，其中最著名的是阿格鲁蒂活黄色（A(vy)）和轴突 1 融合（Axin1(Fu)）小鼠，它们特别适合研究表观遗传学和发育异常之间的这种联系，因为 DNA 甲基化模式的特定变化可以与小鼠中广泛的遗传性病理学相关联。此外，在小鼠和其他动物物种中，都有特定的例子表明，对父母一方的非诱变、环境胁迫，例如接触内分泌干扰化学物质，会导致后代出现意想不到的跨代表型变化。通过体细胞核移植获得的动物也经常表现出与早期胚胎发育过程中核重编程不当相关的病理学，为研究表观遗传学与疾病之间的联系提供了另一种方法。这篇综述将考虑所有这些动物模型如何帮助阐明广泛表型的表观遗传学基础。
