Parp12, a member of the poly-ADP-ribosyl polymerase (PARPs) family, is a mon(ADP-ribosyl) transferase. It is involved in multiple biological processes such as DNA repair, gene expression, RNA processing, ribosome biogenesis, and protein translation through the process of ADP-ribosylation [1,2,3,4]. Genetic models, especially gene knockout (KO) mouse models, have been crucial in understanding its functions.

In mouse oocytes, Parp12 is highly expressed during meiotic maturation. KO of Parp12 leads to abnormal spindle organization, chromosome misalignment, increased aneuploidy, activation of the spindle assembly checkpoint, and attenuation of F-actin, disrupting oocyte meiotic maturation [1]. In thermogenic adipocytes, knockdown of Parp12 reduces UCP1 expression and mitochondrial respiration, highlighting its role in maintaining mitochondrial function [2]. In a model of osteoarthritis (OA), up-regulation of Parp12 by IRF1 promotes cartilage degradation by inhibiting PINK1/Parkin-dependent mitophagy [3]. PARP12 -/- mice show increased replication of a Mac1 mutant coronavirus in bone-marrow-derived macrophages and certain tissues, indicating its role in the antiviral response [4].

In conclusion, Parp12 is essential for oocyte meiotic maturation, mitochondrial function in adipocytes, and plays a role in the antiviral response and OA-related cartilage degradation. The use of Parp12 KO mouse models has been instrumental in revealing its functions in these specific biological processes and disease-related conditions, providing insights into potential therapeutic targets for related diseases.

References:

1. Cao, Guangyi, Guo, Ruirui, Chen, Manqi, Sun, Chuanbo, Wang, Jichang. 2023. PARP12 regulates mouse oocyte meiotic maturation. In Journal of cellular physiology, 238, 1580-1591. doi:10.1002/jcp.31037. https://pubmed.ncbi.nlm.nih.gov/37305966/

2. Hu, Fan, Li, Chang, Ye, Yafen, Li, Xiaohua, Yang, Ying. . PARP12 is required for mitochondrial function maintenance in thermogenic adipocytes. In Adipocyte, 11, 379-388. doi:10.1080/21623945.2022.2091206. https://pubmed.ncbi.nlm.nih.gov/35916471/

3. Deng, Zengfa, Long, Dianbo, Li, Changzhao, Kang, Yan, Mao, Guping. 2024. IRF1-mediated upregulation of PARP12 promotes cartilage degradation by inhibiting PINK1/Parkin dependent mitophagy through ISG15 attenuating ubiquitylation and SUMOylation of MFN1/2. In Bone research, 12, 63. doi:10.1038/s41413-024-00363-3. https://pubmed.ncbi.nlm.nih.gov/39465252/

4. Kerr, Catherine M, Parthasarathy, Srivatsan, Schwarting, Nancy, Orozco, Robin C, Fehr, Anthony R. 2023. PARP12 is required to repress the replication of a Mac1 mutant coronavirus in a cell- and tissue-specific manner. In Journal of virology, 97, e0088523. doi:10.1128/jvi.00885-23. https://pubmed.ncbi.nlm.nih.gov/37695054/