A heterozygous deficiency in protein phosphatase Ppm1b results in an altered ovulation number in mice
A heterozygous deficiency in protein phosphatase Ppm1b results in an altered ovulation number in mice
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DOI：
10.3892/mmr.2019.10194
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发表时间：
2019-06-01
影响因子：
3.4
通讯作者：
Fujii, Junichi
中科院分区：
文献类型：
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作者：
Ishii, Naoki;Homma, Takujiro;Fujii, Junichi
pm 1b是一种金属依赖性丝氨酸/苏氨酸蛋白磷酸酶，催化多种磷酸化蛋白的去磷酸化。Ppm 1b（-/-）小鼠胚胎在受精卵母细胞阶段死亡，而具有C57 BL/6背景的Ppm 1b（+/-）小鼠没有表现出表型异常。由于C57 BL/6品系产生的幼仔数量有限，因此在尝试产生Ppm 1b（-/-）小鼠时，建立了具有ICR背景的同源Ppm 1b（+/-）小鼠，这些小鼠更能生育并产生更多幼仔。然而，结果是，当成对的Ppm 1b（+/-）ICR小鼠再次繁殖时，没有获得Ppm 1b（-/-）后代。从繁殖力的角度分析了Ppm 1b（+/-）雄性和雌性ICR小鼠。Ppm 1b单倍不足对雄性小鼠的睾丸重量或精子数量没有影响。尽管性成熟的Ppm 1b（+/-）小鼠卵巢中的Ppm 1b蛋白水平与Ppm 1b（+/+）小鼠相比有所降低，但在发情期卵巢的组织学外观、窝仔数或血浆孕酮水平方面似乎没有显著差异。当通过使用激素处理的刺激诱导超数排卵时，当发情周期未进行时，4周龄的Ppm 1b（+/-）和Ppm 1b（+/+）小鼠的排卵卵母细胞数相同，然而，与Ppm 1b（+/+）小鼠相比，11周龄时性成熟的Ppm 1b（+/-）小鼠的排卵卵母细胞数较低小鼠在第一和第二超排卵周期。这些结果表明，在Ppm 1b（+/-）小鼠中卵泡发育过度，这导致成熟卵泡的部分耗竭和排卵卵母细胞数量的相应减少。
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.