Frey Wesley D, Kim Joomyeong
Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana, 70803, United States of America.
PLoS One. 2015 Dec 7;10(12):e0144459. doi: 10.1371/journal.pone.0144459. eCollection 2015.
Paternally Expressed Gene 3 (Peg3) is an imprinted gene that controls milk letdown and maternal-caring behaviors. In this study, a conditional knockout allele has been developed in Mus musculus to further characterize these known functions of Peg3 in a tissue-specific manner. The mutant line was first crossed with a germline Cre. The progeny of this cross displayed growth retardation phenotypes. This is consistent with those seen in the previous mutant lines of Peg3, confirming the usefulness of the new mutant allele. The mutant line was subsequently crossed individually with MMTV- and Nkx2.1-Cre lines to test Peg3's roles in the mammary gland and hypothalamus, respectively. According to the results, the milk letdown process was impaired in the nursing females with the Peg3 mutation in the mammary gland, but not in the hypothalamus. This suggests that Peg3's roles in the milk letdown process are more critical in the mammary gland than in the hypothalamus. In contrast, one of the maternal-caring behaviors, nest-building, was interrupted in the females with the mutation in both MMTV- and Nkx2.1-driven lines. Overall, this is the first study to introduce a conditional knockout allele of Peg3 and to further dissect its contribution to mammalian reproduction in a tissue-specific manner.
父源表达基因3（Peg3）是一个印记基因，它控制乳汁排出和母性行为。在本研究中，已在小家鼠中构建了一个条件性敲除等位基因，以组织特异性方式进一步表征Peg3的这些已知功能。首先将突变系与生殖系Cre进行杂交。该杂交后代表现出生长迟缓的表型。这与之前Peg3突变系中观察到的表型一致，证实了新突变等位基因的有效性。随后将突变系分别与MMTV-Cre和Nkx2.1-Cre系杂交，以分别测试Peg3在乳腺和下丘脑中的作用。结果显示，乳腺中携带Peg3突变的哺乳雌性动物的乳汁排出过程受损，但在下丘脑中未受损。这表明Peg3在乳汁排出过程中的作用在乳腺中比在下丘脑中更为关键。相比之下，在MMTV-和Nkx2.1驱动的品系中携带突变的雌性动物的一种母性行为——筑巢行为受到了干扰。总体而言，这是首次引入Peg3条件性敲除等位基因并以组织特异性方式进一步剖析其对哺乳动物繁殖贡献的研究。
