Gsdma3, a member of the gasdermin family, is related to mitochondrial metabolism and involved in immune responses. It is also known to be involved in apoptosis-related pathways and is expressed in specific tissues like skin keratinocytes, gastrointestinal tract, and mammary glands [1,3]. It plays a role in maintaining the balance of cellular metabolism and is crucial for normal development and function in certain tissues [1]. Genetic mouse models are valuable tools for studying its function.

Gsdma3 deficiency in mice reprograms B cell metabolism, upregulating PI3K-Akt-mTOR signaling, and impairs BCR signaling, yet has no impact on B cell development and humoral immunity, potentially due to compensation by GSDMA2 [1]. In mammary gland development, Gsdma3-mutated (AE) mice show smaller mammary glands with shorter ductal extension, less bifurcation, and abnormal immune reactions in the glands [2]. In hair follicle differentiation, Gsdma3-deficient mice (AE mice) exhibit abnormal hair structures and reduced hair keratins, with a genetic pathway of Msx2/Foxn1/acidic hair keratin involved [4]. Gsdma3-mutant mice also show abnormal catagen phase in the hair follicle cycle, with decreased apoptosis and Caspase-3 expression, which can be rescued by injecting Gsdma3 plasmid [5]. Depletion of Gsdma1/2/3 in mice alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR-Stat3/Akt pathway [6].

In summary, Gsdma3 is essential for multiple biological processes including B cell metabolism regulation, mammary gland development, hair follicle differentiation, and hair follicle cycle regulation. The use of Gsdma3-KO or related gene-depleted mouse models has revealed its roles in these processes, contributing to our understanding of related physiological functions and potentially associated diseases such as skin diseases and immune-related disorders.

References:

1. Guan, Fei, Luo, Xi, Liu, Ju, Liu, Chaohong, Lei, Jiahui. 2023. GSDMA3 deficiency reprograms cellular metabolism and modulates BCR signaling in murine B cells. In iScience, 26, 107341. doi:10.1016/j.isci.2023.107341. https://pubmed.ncbi.nlm.nih.gov/37539041/

2. Guo, Haiying, Xu, Senlin, Liu, Yingxin, Lian, Xiaohua, Li, Yuhong. 2017. Gsdma3 is required for mammary gland development in mice. In Histochemistry and cell biology, 147, 575-583. doi:10.1007/s00418-017-1542-z. https://pubmed.ncbi.nlm.nih.gov/28168650/

3. Lei, Mingxing, Bai, Xiufeng, Yang, Tian, Yang, Li, Lian, Xiaohua. 2012. Gsdma3 is a new factor needed for TNF-α-mediated apoptosis signal pathway in mouse skin keratinocytes. In Histochemistry and cell biology, 138, 385-96. doi:10.1007/s00418-012-0960-1. https://pubmed.ncbi.nlm.nih.gov/22585037/

4. Li, Jin, Zhou, Yue, Yang, Tian, Lian, Xiaohua, Yang, Li. 2010. Gsdma3 is required for hair follicle differentiation in mice. In Biochemical and biophysical research communications, 403, 18-23. doi:10.1016/j.bbrc.2010.10.094. https://pubmed.ncbi.nlm.nih.gov/20977888/

5. Lei, Mingxing, Gao, Xiang, Yang, Li, Yang, Tian, Lian, Xiaohua. 2011. Gsdma3 gene is needed for the induction of apoptosis-driven catagen during mouse hair follicle cycle. In Histochemistry and cell biology, 136, 335-43. doi:10.1007/s00418-011-0845-8. https://pubmed.ncbi.nlm.nih.gov/21805153/

6. Liu, Qiyao, Li, Manyun, Sun, Minli, Gao, Xiang, Lin, Zhaoyu. . Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR-Stat3/Akt pathway. In Journal of molecular cell biology, 16, . doi:10.1093/jmcb/mjad080. https://pubmed.ncbi.nlm.nih.gov/38115633/