Cyp4v3 is the murine ortholog of human CYP4V2, an orphan cytochrome P450 enzyme with its function, expression sites, and regulation not fully elucidated [3]. Its biological importance is linked to lipid metabolism, as mutations in its human counterpart, CYP4V2, cause Bietti crystalline corneoretinal dystrophy (BCD), suggesting Cyp4v3 may play a role in related lipid-associated pathways. Mouse models are valuable for studying Cyp4v3.

In Cyp4v3 knockout (KO) mouse models, characteristic features of BCD recur, such as retinal crystalline deposits, atrophy and degeneration of retinal pigment epithelium (RPE) cells, and decline in electroretinogram (ERG) amplitude, mimicking the human disease progression with age [1]. Lipid profiling in Cyp4v3 KO mice shows increased levels of polyunsaturated fatty acids (PUFAs) in RPE, and transcriptome analysis reveals changes in genes involved in iron homeostasis, with upregulation of NCOA4. Ferroptosis-related characteristics like mitochondrial defects, lipid peroxidation, ROS accumulation, and upregulation of related genes are detected in RPE both in vitro and in vivo [2]. High-fat diet (HFD) exacerbates the retinal degeneration and lipid accumulation in Cyp4v3 KO mice, similar to BCD phenotype [2].

In conclusion, Cyp4v3 is crucial in maintaining normal retinal function, likely through its role in lipid and iron metabolism. The Cyp4v3 KO mouse models have significantly contributed to understanding the pathogenesis of BCD, providing insights into potential therapeutic strategies for this currently untreatable autosomal recessive chorioretinal degenerative disease [1-3].

References:

1. Jia, R X, Jiang, S W, Zhao, L, Yang, L P. . [Generation and characterization of Cyp4v3 gene knockout mice]. In Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences, 53, 1099-1106. doi:. https://pubmed.ncbi.nlm.nih.gov/34916689/

2. Shen, Chang, Yang, Qianjie, Chen, Kuangqi, Shen, Ye, Cui, Hongguang. 2024. Uncovering the role of ferroptosis in Bietti crystalline dystrophy and potential therapeutic strategies. In Cell communication and signaling : CCS, 22, 359. doi:10.1186/s12964-024-01710-x. https://pubmed.ncbi.nlm.nih.gov/38992691/

3. Stark, Katarina, Guengerich, F Peter. . Characterization of orphan human cytochromes P450. In Drug metabolism reviews, 39, 627-37. doi:. https://pubmed.ncbi.nlm.nih.gov/17786643/