Abstract

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.

Highlights

  • Expressed Gene 3 (Peg3) is an imprinted gene located on human chromosome 19q13.4 and mouse chromosome 7qA1 [1,2]

  • The potential roles of Paternally Expressed Gene 3 (Peg3) in diseases ranging from low birth-weight to breast and cervical cancer have triggered the production of mutant mouse lines, which have been studied for multiple characteristics

  • In order to test when and where Peg3 expression is required for proper growth and development, two new mouse lines have been generated, Peg3FlpKO and Peg3DelKO (Fig 1A)

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Summary

Introduction

Expressed Gene 3 (Peg3) is an imprinted gene located on human chromosome 19q13.4 and mouse chromosome 7qA1 [1,2]. Peg encodes a protein with DNA-binding capabilities that is localized to the nucleus of neuronal cells [3,4]. Expression of Peg is most dominant in the ovary, placenta and hypothalamus as observed in murine models [2,5]. The potential roles of Peg in diseases ranging from low birth-weight to breast and cervical cancer have triggered the production of mutant mouse lines, which have been studied for multiple characteristics. The most striking and consistent characteristics observed in a previous Peg knock-in line is a maternal caring problem in Peg3-deficient dams and a growth defect in neonatal pups [5,6,7]. Our group has generated a mouse line with a deletion in the promoter region as well as a strain carrying a transcriptional truncation, which were both reported to have similar effects [8,9]

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