A heterozygous deficiency in protein phosphatase Ppm1b results in an altered ovulation number in mice

Ishii,Naoki; Homma,Takujiro; Watanabe,Ren; Kimura,Naoko; Ohnishi,Motoko; Kobayashi,Takayasu; Fujii,Junichi

doi:10.3892/mmr.2019.10194

A heterozygous deficiency in protein phosphatase Ppm1b results in an altered ovulation number in mice

Authors:
- Naoki Ishii
- Takujiro Homma
- Ren Watanabe
- Naoko Kimura
- Motoko Ohnishi
- Takayasu Kobayashi
- Junichi Fujii
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Affiliations: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata, Yamagata 990‑9585, Japan, Laboratory of Animal Reproduction, Graduate School of Agricultural Sciences, Yamagata University, Tsuruoka, Yamagata 997‑8555, Japan, Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi 87‑8501, Japan, Center for Gene Research, Tohoku University, Sendai, Miyagi 980‑8575, Japan
Published online on: April 25, 2019 https://doi.org/10.3892/mmr.2019.10194
Pages: 5353-5360

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Abstract

Ppm1b, a metal‑dependent serine/threonine protein phosphatase, catalyzes the dephosphorylation of a variety of phosphorylated proteins. Ppm1b‑/‑ mouse embryos die at the fertilized oocyte stage, whereas Ppm1b+/‑ mice with a C57BL/6 background exhibit no phenotypic abnormalities. Because the C57BL/6 strain produces a limited number of pups, in an attempt to produce Ppm1b‑/‑ mice, congenic Ppm1b+/‑ mice with an ICR background were established, which are more fertile and gave birth to more pups. As a result, however, no Ppm1b‑/‑ offspring were obtained when pairs of Ppm1b+/‑ ICR mice were bred again. Ppm1b+/‑ male and female ICR mice were analyzed from the viewpoint of fecundity. The Ppm1b haploinsufficiency had no effect on testicular weight or the number of sperm in male mice. Despite the fact that the levels of Ppm1b protein in the ovaries of sexually mature Ppm1b+/‑ mice were decreased compared with those of Ppm1b+/+ mice, there appeared to be no significant difference in the histological appearance of the ovaries, litter sizes or plasma progesterone levels at the estrous stage. When superovulation was induced by stimulation using a hormone treatment, the number of ovulated oocytes were the same for Ppm1b+/‑ and Ppm1b+/+ mice at 4 weeks of age when the estrous cycle did not proceed, however, the number of ovulated oocytes was lower in sexually mature Ppm1b+/‑ mice at 11 weeks of age compared with Ppm1b+/+ mice in the first and the second superovulation cycles. These collective results suggest that follicle development is excessive in Ppm1b+/‑ mice, and that this leads to a partial depletion of matured follicles and a corresponding decrease in the number of ovulated oocytes.

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