Prkcd-KO Mouse

Prkcd, also known as Protein kinase C delta, is a member of the PKC family. It has diverse biological properties and is involved in multiple biological processes. It participates in pathways related to immune response, cell apoptosis, mitochondrial function, and cell signaling, playing a crucial role in maintaining normal physiological functions [1,2,3]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying Prkcd's functions in vivo.

In chronic obstructive pulmonary disease (COPD), Prkcd promotes inflammatory response, apoptosis, mitochondrial dysfunction, and MUC5AC hypersecretion, suggesting it could be a potential therapeutic target [1]. Protein kinase C δ (PKCδ) deficiency, caused by mutations in Prkcd, is a rare genetic disorder. Patients show phenotypic variability, including autoimmune lymphoproliferative syndrome-related syndromes and infection susceptibility, highlighting the role of Prkcd in immune tolerance and effector functions against pathogens [2]. In PRKN-independent mitophagy, both GAK and Prkcd are positive regulators. Knockdown of GAK homologue in C. elegans or knockout of Prkcd homologues in zebrafish significantly inhibits basal mitophagy, demonstrating the in vivo relevance of Prkcd in mitophagy regulation [3]. In gastric cancer, TRIM69 suppresses anoikis resistance and metastasis through ubiquitin-proteasome-mediated degradation of Prkcd [4]. In triple negative breast cancer (TNBC), PRKCD_pY313 activates Src and p38 MAPK to promote TNBC progression [5]. In the Chinese Han population, PRKCD polymorphisms are associated with Vogt-Koyanagi-Harada disease susceptibility [6].

In conclusion, Prkcd is essential in various biological processes including immune response, mitophagy, and cell survival and metastasis in cancer. Studies using KO/CKO models in different organisms have revealed its role in diseases such as COPD, autoimmune disorders, and multiple cancers, providing insights into potential therapeutic strategies for these conditions.

References:

1. Li, Siqi, Huang, Qiong, Zhou, Dongbo, He, Baimei. 2022. PRKCD as a potential therapeutic target for chronic obstructive pulmonary disease. In International immunopharmacology, 113, 109374. doi:10.1016/j.intimp.2022.109374. https://pubmed.ncbi.nlm.nih.gov/36279664/

2. Jefferson, Lucy, Ramanan, Athimalaipet Vaidyanathan, Jolles, Stephen, Belot, Alexandre, Roderick, Marion Ruth. 2023. Phenotypic Variability in PRKCD: a Review of the Literature. In Journal of clinical immunology, 43, 1692-1705. doi:10.1007/s10875-023-01579-4. https://pubmed.ncbi.nlm.nih.gov/37794137/

3. Munson, Michael J, Mathai, Benan J, Ng, Matthew Yoke Wui, Fang, Evandro F, Simonsen, Anne. 2021. GAK and PRKCD are positive regulators of PRKN-independent mitophagy. In Nature communications, 12, 6101. doi:10.1038/s41467-021-26331-7. https://pubmed.ncbi.nlm.nih.gov/34671015/

4. Sun, Linqing, Chen, Yuqi, Xia, Lu, Shi, Tongguo, Chen, Weichang. 2023. TRIM69 suppressed the anoikis resistance and metastasis of gastric cancer through ubiquitin‒proteasome-mediated degradation of PRKCD. In Oncogene, 42, 3619-3632. doi:10.1038/s41388-023-02873-6. https://pubmed.ncbi.nlm.nih.gov/37864033/

5. Deng, Yujiao, Hou, Zhanwu, Li, Yizhen, Liu, Huadong, Dai, Zhijun. 2024. Superbinder based phosphoproteomic landscape revealed PRKCD_pY313 mediates the activation of Src and p38 MAPK to promote TNBC progression. In Cell communication and signaling : CCS, 22, 115. doi:10.1186/s12964-024-01487-z. https://pubmed.ncbi.nlm.nih.gov/38347536/

6. Zhou, Chunya, Cai, Shiya, Xie, Yuhong, Yang, Peizeng, Hu, Jianmin. 2023. Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population. In Human genomics, 17, 9. doi:10.1186/s40246-023-00459-7. https://pubmed.ncbi.nlm.nih.gov/36782298/