TMEM232, transmembrane protein 232, is associated with multiple biological functions and disease processes. It has been implicated in pathways related to inflammation and sperm development. Its study through genetic models like knockout mice can provide insights into its roles in vivo [1,2,3].

In atopic dermatitis (AD), TMEM232 was found to be associated with the disease through genome-wide association and fine-mapping studies. In AD, its expression is increased in patient skin lesions, an AD mouse model, and in keratinocytes stimulated with inflammatory factors. Tmem232 knockout (Tmem232-/-) mice showed reduced dermatitis severity, mast-cell infiltration, and Th1 and Th2-related inflammatory factor expression in skin tissue compared to wild-type mice. TMEM232 exacerbates the inflammation response in AD via the nuclear factor-κB and signal transducer and activator of transcription (STAT) 3 pathways, and is regulated by the interleukin-4/STAT6 axis. Topical application of Tmem232 siRNA ameliorated AD-like lesions [1].

In male fertility, Tmem232-/-male mice were infertile with immotile sperm and morphological flagellar defects. Electron microscopy revealed abnormal midpiece-principal junctions and loss of the fourth outer microtubule doublet in sperm. Proteomic analysis showed altered expression of proteins related to flagellar motility and sperm capacitation. TMEM232 was also found to be involved in autophagy during spermiogenesis [2]. Another study also reported that Tmem232 knockout mice had male-specific infertility due to failure of cytoplasm removal and absence of the 7th outer microtubule doublet with its corresponding outer dense fiber in spermatozoa flagella, and TMEM232 interacts with ODF1, essential for sperm motility [3].

In conclusion, TMEM232 plays a crucial role in regulating inflammation in atopic dermatitis and is essential for the formation of sperm flagellum and male fertility. The use of Tmem232 knockout mouse models has significantly contributed to understanding its functions in these disease areas and biological processes [1,2,3].

References:

1. Han, Jie, Cai, Xinying, Qin, Shichun, Fang, Wenliang, Xiao, Fengli. . TMEM232 promotes the inflammatory response in atopic dermatitis via the nuclear factor-κB and signal transducer and activator of transcription 3 signalling pathways. In The British journal of dermatology, 189, 195-209. doi:10.1093/bjd/ljad078. https://pubmed.ncbi.nlm.nih.gov/36928730/

2. Cai, Xinying, Zhang, Hui, Kong, Shuai, Xiao, Fengli, Wang, Fengsong. 2024. TMEM232 is required for the formation of sperm flagellum and male fertility in mice. In Cell death & disease, 15, 806. doi:10.1038/s41419-024-07200-9. https://pubmed.ncbi.nlm.nih.gov/39516485/

3. He, Xiuqing, Mu, Wenyu, Wang, Ziqi, Lv, Yue, Liu, Shangming. 2023. Deficiency of the Tmem232 Gene Causes Male Infertility with Morphological Abnormalities of the Sperm Flagellum in Mice. In Cells, 12, . doi:10.3390/cells12121614. https://pubmed.ncbi.nlm.nih.gov/37371084/