Zdhhc17-KO Mouse

Zdhhc17, a member of the zinc finger DHHC-domain containing (ZDHHC) family, is an S-acyltransferase enzyme. It is involved in S-palmitoylation, a post-translational modification process that plays crucial roles in various cellular functions such as protein trafficking, membrane association, and signal transduction. Zdhhc17 is associated with multiple biological pathways and is of great biological importance in processes like nervous system development, metabolic regulation, and endocrine function [1,4]. Genetic models, especially knockout (KO) mouse models, have been valuable in studying Zdhhc17.

In a high-fat diet-induced liver tumorigenesis study, Zdhhc17 knockout mice were used. The results showed that Zdhhc17, along with Zdhhc24, palmitoylates AKT, promoting its activation and thus driving NASH and liver cancer development. This indicates that Zdhhc17 is involved in the PI3K-AKT pathway in the context of liver tumorigenesis [2]. In polycystic ovary syndrome (PCOS) research, ovarian ZDHHC17 expression was found to be attenuated in patients. In vitro and in vivo experiments showed that Zdhhc17 depletion decreased HSP90α palmitoylation levels and hampered the conversion of androgen to estrogen via CYP19A1, suggesting its role in PCOS pathophysiology [3].

In conclusion, Zdhhc17 is essential for multiple biological processes. Through model-based research, especially using KO mouse models, it has been shown to play important roles in diseases such as liver cancer and PCOS. These findings provide insights into the pathophysiological mechanisms of these diseases and suggest Zdhhc17 as a potential therapeutic target.

References:

1. Zhang, Ying, Fan, Sisi, He, Lu, Li, Lanfang. 2024. The ZDHHC13/ZDHHC17 subfamily: From biological functions to therapeutic targets of diseases. In Pharmacological research, 209, 107418. doi:10.1016/j.phrs.2024.107418. https://pubmed.ncbi.nlm.nih.gov/39306022/

2. Bu, Lang, Zhang, Zhengkun, Chen, Jianwen, Kuang, Ming, Guo, Jianping. 2024. High-fat diet promotes liver tumorigenesis via palmitoylation and activation of AKT. In Gut, 73, 1156-1168. doi:10.1136/gutjnl-2023-330826. https://pubmed.ncbi.nlm.nih.gov/38191266/

3. Zhao, Shanmeizi, Ma, Rujun, Jueraitetibaike, Kadiliya, Yao, Bing, Guo, Zhigang. 2023. ZDHHC17 participates in the pathogenesis of polycystic ovary syndrome by affecting androgen conversion to estrogen in granulosa cells. In Molecular and cellular endocrinology, 578, 112076. doi:10.1016/j.mce.2023.112076. https://pubmed.ncbi.nlm.nih.gov/37769867/

4. Shi, Wei, Wang, Fen, Gao, Ming, Chen, Xueran, Hao, Aijun. 2015. ZDHHC17 promotes axon outgrowth by regulating TrkA-tubulin complex formation. In Molecular and cellular neurosciences, 68, 194-202. doi:10.1016/j.mcn.2015.07.005. https://pubmed.ncbi.nlm.nih.gov/26232532/