雄性Padi2/Padi4双敲除小鼠的青春期延迟、促性腺激素异常和生育能力低下。

Kelly L Sams, Chinatsu Mukai, Brooke A Marks, Chitvan Mittal, Elena Alina Demeter, Sophie Nelissen, Jennifer K Grenier, Ann E Tate, Faraz Ahmed, Scott A Coonrod
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引用次数: 4

摘要

背景:肽精氨酸脱亚胺酶(PADs)在一个称为瓜氨酸化或脱亚胺化的过程中将精氨酸残基转化为瓜氨酸。最近,两种pad, PAD2和PAD4,已经在体外与激素信号传导有关,本研究的目的是测试PAD2/PAD4与体内激素信号传导之间的联系。方法:初步分析Padi2和Padi4单敲除(SKO)小鼠未发现任何明显的生殖缺陷,我们预测这可能是由于遗传补偿。为了验证这一假设,我们建立了Padi2/Padi4双敲除(DKO)小鼠模型,并与野生型FVB/NJ (WT)和两种SKO小鼠一起测试了这些小鼠的一系列生殖缺陷。结果:对照育种试验发现,雄性DKO小鼠比WT对照组似乎需要更长的时间才能生下第一胎。当这些小鼠与DKO或WT雌性交配时,这种趋势保持不变。此外,无性别的2天大的DKO幼崽和雄性DKO断奶崽的体重都明显低于WT同类,进入青春期的时间明显长于WT雄性,血清睾酮水平也一直较低。此外,90日龄成年DKO雄性的睾丸比WT雄性小,生殖细胞凋亡率增加。结论:Padi2/Padi4 DKO小鼠模型为研究PAD功能提供了新的工具,我们的研究结果首次提供了PAD与激素信号传导联系的体内证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice.

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice.

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice.

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice.

Background: Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo.

Methods: Preliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created a Padi2/Padi4 double knockout (DKO) mouse model and tested these mice along with wild-type FVB/NJ (WT) and both strains of SKO mice for a range of reproductive defects.

Results: Controlled breeding trials found that male DKO mice appeared to take longer to have their first litter than WT controls. This tendency was maintained when these mice were mated to either DKO or WT females. Additionally, unsexed 2-day old DKO pups and male DKO weanlings both weighed significantly less than their WT counterparts, took significantly longer than WT males to reach puberty, and had consistently lower serum testosterone levels. Furthermore, 90-day old adult DKO males had smaller testes than WT males with increased rates of germ cell apoptosis.

Conclusions: The Padi2/Padi4 DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the first in vivo evidence linking PADs with hormone signaling.

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