Ccdc92-KO Mouse

CCDC92, a member of the coiled-coil domain-containing protein family, has been implicated in lipid metabolism, coronary heart disease, type 2 diabetes, and potentially anxiety [3,4,5,6,7]. It may be involved in adipocyte differentiation and is associated with metabolic disorders and insulin resistance [3,4]. Genetic models, such as knockout mice, have been crucial for studying its functions.

In mouse models, Ccdc92 whole-body knockout (KO) reduces obesity and increases insulin sensitivity under high-fat diet conditions, inhibits macrophage infiltration and fibrosis in white adipose tissue, increases energy expenditure, and attenuates hepatic steatosis [4]. Podocyte-specific Ccdc92 knockout (CKO) in diabetic mice (db/db and HFD/STZ models) ameliorates podocyte injury and ectopic lipid deposition. Mechanistically, CCDC92 promotes podocyte lipotoxicity, at least in part through ABCA1 signaling-mediated lipid homeostasis, and it also promotes the degradation of ABCA1 by regulating PA28α-mediated proteasome activity, reducing cholesterol efflux and finally promoting podocyte injury [1,2].

In conclusion, CCDC92 plays a significant role in metabolism, especially in lipid homeostasis. KO and CKO mouse models have revealed its contributions to obesity, insulin resistance, and diabetic kidney disease, suggesting that it could be a potential biomarker and therapeutic target for these conditions [1,2,4].

References:

1. Zuo, Fuwen, Wang, Youzhao, Xu, Xinlei, Wang, Ziying, Yi, Fan. 2023. CCDC92 deficiency ameliorates podocyte lipotoxicity in diabetic kidney disease. In Metabolism: clinical and experimental, 150, 155724. doi:10.1016/j.metabol.2023.155724. https://pubmed.ncbi.nlm.nih.gov/37952690/

2. Zuo, Fu-Wen, Liu, Zhi-Yong, Wang, Ming-Wei, Wang, Zi-Ying, Yi, Fan. 2024. CCDC92 promotes podocyte injury by regulating PA28α/ABCA1/cholesterol efflux axis in type 2 diabetic mice. In Acta pharmacologica Sinica, 45, 1019-1031. doi:10.1038/s41401-023-01213-4. https://pubmed.ncbi.nlm.nih.gov/38228909/

3. Lotta, Luca A, Gulati, Pawan, Day, Felix R, O'Rahilly, Stephen, Scott, Robert A. 2016. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. In Nature genetics, 49, 17-26. doi:10.1038/ng.3714. https://pubmed.ncbi.nlm.nih.gov/27841877/

4. Ren, Lu, Du, Wa, Song, Dan, Becker, Richard C, Fan, Yanbo. 2022. Genetic ablation of diabetes-associated gene Ccdc92 reduces obesity and insulin resistance in mice. In iScience, 26, 105769. doi:10.1016/j.isci.2022.105769. https://pubmed.ncbi.nlm.nih.gov/36594018/

5. Tang, Haibo, Wang, Jie, Deng, Peizhi, Zhu, Shaihong, Lu, Yao. 2023. Transcriptome-wide association study-derived genes as potential visceral adipose tissue-specific targets for type 2 diabetes. In Diabetologia, 66, 2087-2100. doi:10.1007/s00125-023-05978-5. https://pubmed.ncbi.nlm.nih.gov/37540242/

6. Huang, Lam O, Rauch, Alexander, Mazzaferro, Eugenia, Kilpeläinen, Tuomas O, Loos, Ruth J F. 2021. Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities. In Nature metabolism, 3, 228-243. doi:10.1038/s42255-021-00346-2. https://pubmed.ncbi.nlm.nih.gov/33619380/

7. Jin, Xing, Dong, Shuangshuang, Yang, Yang, Bao, Guangyu, Ma, Haochuan. 2024. Nominating novel proteins for anxiety via integrating human brain proteomes and genome-wide association study. In Journal of affective disorders, 358, 129-137. doi:10.1016/j.jad.2024.04.097. https://pubmed.ncbi.nlm.nih.gov/38697224/