Wip1基因对动物繁殖及免疫的调节作用

野生型p53诱导的磷酸酶1（wild-type p53-induced phosphatase 1，Wip1）是蛋白磷酸酶2C （protein phosphatase type 2C，PP2C）家族中的一员，可以靶向调控机体内多种重要的信号分子，如p53、MAPK和Chk1/Chk2等，在动物细胞周期、增殖、分化、凋亡、衰老、自噬及DNA损伤修复等生理过程中发挥重要作用。Wip1基因缺失会使小鼠生殖激素水平失衡，且该基因通过ATM、Wnt、凋亡和炎症等信号通路影响精子生成过程，导致雄性动物繁殖力下降。此外，Wip1基因还可通过动态平衡调节DNA损伤反应和去磷酸化作用来影响卵母细胞和胚胎发育，从而调控雌性动物的生殖。免疫系统是机体执行免疫应答及免疫功能的重要系统，其与炎症反应和肿瘤发生有着紧密的联系。Wip1基因缺失会使病原体敏感性增强，影响T细胞、B细胞和中性粒细胞迁移及凋亡，进而导致炎症反应。作为原癌基因，Wip1基因通过调控各种信号分子影响DNA损伤修复、细胞周期进程及细胞凋亡等，参与肿瘤发生。因此，Wip1基因在动物繁殖调控和免疫调节中扮演着重要角色。目前，Wip1基因受到越来越多学者的关注，特别是其调控动物疾病发生发展的机制已成为研究热点。本研究主要综述了Wip1基因对动物繁殖及免疫的调节作用，以期为家畜育种、疾病防治及靶向治疗提供新思路。

Regulation of Wip1 Gene on Animal Reproduction and Immunity

Wild-type p53-induced phosphatase 1(Wip1) is a member of protein phosphatase 2C (PP2C) family, which regulates a number of critical signal molecules, such as p53, MAPK and Chk1/Chk2, and so on, it plays an important role in physiological and pathological processes of cell cycle, proliferation, differentiation, apoptosis, senescence, autophagy and DNA damage repair in animal.With the rapid development of molecular biology, many studies have reported that the deletion of Wip1 gene will imbalance the level of reproductive hormones in mice, and it affects spermatogenesis by regulating signal pathways such as ATM, Wnt, apoptosis and inflammation, resulting in the decrease of animal fecundity.In addition, Wip1 gene also regulates DNA damage response and dephosphorylation through dynamic balance to affect oocyte and embryonic development, so as to regulate the reproduction of female animals.The immune system is an important system in the body to perform immune response and immune function, and it is closely related to tumorigenesis.Knock-out Wip1 gene will also increase the sensitivity to pathogens, affect the migration and apoptosis of T cells, B cells and neutrophils, and lead to inflammation.As a proto-oncogene, Wip1 gene also participates in tumorigenesis by regulating various signal molecules, affecting DNA damage repair, cell cycle progression and apoptosis.Therefore, Wip1 gene plays an important role in biological processes such as animal reproductive regulation and immune inflammation.At present, Wip1 gene has been attracting more and more attention, especially its mechanism of regulating the occurrence and development of animal diseases has become a research hotspot.This study mainly reviewed the regulatory effect of Wip1 gene on animal reproduction and immune, in order to provide new ideas for livestock breeding, disease prevention and targeted therapy