Gpx6-KO Mouse

Gpx6, a member of the glutathione peroxidase family, is a selenoprotein enzyme. Glutathione peroxidases play crucial roles in maintaining redox balance by catalyzing the reduction of H2O2 or organic hydroperoxides to water or corresponding alcohols [3]. Gpx6's exact functions were once unknown, but recent research has started to shed light on its roles in biological processes [1].

In porcine sperm, GPx6 is present in testis, epididymis, accessory sex glands, sperm and seminal plasma. Incubating capacitated sperm with a GPx6 antibody improved sperm vitality, increased sperm capacitation and acrosome reaction, as well as the cAMP concentration in sperm. It also increased H2O2 concentration while decreasing the expression of SOD3 and CAT, suggesting it may prevent premature sperm capacitation by affecting the antioxidant pathway [2]. In a high fat high fructose diet-induced non-alcoholic steatohepatitis (NASH) mouse model, PGAM5 deficiency led to increased expression of Gpx6, which was associated with reduced hepatic steatosis and inflammation [4]. In a Huntington's disease mouse model, overexpression of Gpx6 alleviated both behavioral and molecular phenotypes associated with the disease [5].

In summary, Gpx6 appears to be involved in processes such as sperm function, redox-related regulation in NASH, and modulation of Huntington's disease phenotypes. Studies using animal models like mice have been crucial in uncovering these functions, providing insights into its role in specific biological processes and disease conditions.

References:

1. Brigelius-Flohé, Regina, Maiorino, Matilde. 2012. Glutathione peroxidases. In Biochimica et biophysica acta, 1830, 3289-303. doi:10.1016/j.bbagen.2012.11.020. https://pubmed.ncbi.nlm.nih.gov/23201771/

2. Chen, Yun, Wang, Kai, Zhang, Delong, Wu, Zhenfang, Zhang, Shouquan. 2020. GPx6 is involved in the in vitro induced capacitation and acrosome reaction in porcine sperm. In Theriogenology, 156, 107-115. doi:10.1016/j.theriogenology.2020.06.020. https://pubmed.ncbi.nlm.nih.gov/32698036/

3. Pei, Jun, Pan, Xingyu, Wei, Guanghui, Hua, Yi. 2023. Research progress of glutathione peroxidase family (GPX) in redoxidation. In Frontiers in pharmacology, 14, 1147414. doi:10.3389/fphar.2023.1147414. https://pubmed.ncbi.nlm.nih.gov/36937839/

4. Li, Li, Guo, Chengcheng, Yu, Yue, Ji, Linong, Zou, Xiantong. 2023. Differential effects of PGAM5 knockout on high fat high fructose diet and methionine choline-deficient diet induced non-alcoholic steatohepatitis (NASH) in mice. In Cell & bioscience, 13, 154. doi:10.1186/s13578-023-01095-3. https://pubmed.ncbi.nlm.nih.gov/37605246/

5. Shema, Reut, Kulicke, Ruth, Cowley, Glenn S, Root, David E, Heiman, Myriam. 2014. Synthetic lethal screening in the mammalian central nervous system identifies Gpx6 as a modulator of Huntington's disease. In Proceedings of the National Academy of Sciences of the United States of America, 112, 268-72. doi:10.1073/pnas.1417231112. https://pubmed.ncbi.nlm.nih.gov/25535386/