Nlrp14-KO Mouse

Nlrp14, a member of the NOD-like receptor (NLR) family, is preferentially expressed in mammalian oocytes, early embryos, and germ cells. It plays crucial roles in processes like oocyte-to-embryo transition, oocyte maturation, germ cell differentiation, and spermatogenesis, and is associated with regulating innate immune responses during fertilization [1,2,3,4].

Gene knockout studies in mice have revealed its significance. Maternal loss of Nlrp14 leads to female sterility with oocyte maturation defects and early embryonic arrest. It is essential for maintaining calcium homeostasis during oocyte-to-embryo transition by regulating the K27 ubiquitination of Nclx, a mitochondrial Na+/Ca2+ exchanger. In male mice, Nlrp14 knockout inhibits spermatogonial stem cell differentiation and meiosis, resulting in severe oligozoospermia and sperm abnormality. Also, it negatively regulates cytosolic nucleic acid sensing during fertilization by targeting TBK1 for ubiquitination and degradation [1,2,3,4].

In conclusion, Nlrp14 is vital for reproductive processes in both male and female mice. Its study through gene knockout mouse models has provided insights into its role in early embryonic development, oocyte maturation, and spermatogenesis, which may have implications for understanding and treating infertility in humans [1,2,3].

References:

1. Meng, Tie-Gang, Guo, Jia-Ni, Zhu, Liu, Li, Zhonghan, Sun, Qing-Yuan. 2023. NLRP14 Safeguards Calcium Homeostasis via Regulating the K27 Ubiquitination of Nclx in Oocyte-to-Embryo Transition. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2301940. doi:10.1002/advs.202301940. https://pubmed.ncbi.nlm.nih.gov/37493331/

2. Zhang, Wenzhe, Zhang, Rongrong, Wu, Ling, Qin, Yingying, Jiao, Xue. 2023. NLRP14 deficiency causes female infertility with oocyte maturation defects and early embryonic arrest by impairing cytoplasmic UHRF1 abundance. In Cell reports, 42, 113531. doi:10.1016/j.celrep.2023.113531. https://pubmed.ncbi.nlm.nih.gov/38060382/

3. Yin, Yike, Cao, Shiyu, Fu, Huancheng, Sun, Qing-Yuan, Li, Zhonghan. 2020. A noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis. In Proceedings of the National Academy of Sciences of the United States of America, 117, 22237-22248. doi:10.1073/pnas.2005533117. https://pubmed.ncbi.nlm.nih.gov/32839316/

4. Abe, Takayuki, Lee, Albert, Sitharam, Ramaswami, Rabadan, Raul, Shapira, Sagi D. . Germ-Cell-Specific Inflammasome Component NLRP14 Negatively Regulates Cytosolic Nucleic Acid Sensing to Promote Fertilization. In Immunity, 46, 621-634. doi:10.1016/j.immuni.2017.03.020. https://pubmed.ncbi.nlm.nih.gov/28423339/