Cyp39a1-flox Mouse

CYP39A1, a member of the cytochrome P450 family, functions as an oxysterol 7α -hydroxylase, selectively catalyzing the 7α -hydroxylation of 24 -hydroxycholesterol [8,9]. It is involved in the alternative bile acid synthesis pathway in the liver and is also expressed in the ciliary nonpigmented epithelium of the eye, suggesting a role in ocular sterol metabolism [9]. It may be regulated by the orphan nuclear receptor RORα, and abnormal expression can lead to the accumulation of 24S -OHC, influencing neurodegenerative disease-related deterioration [7].

In hepatocellular carcinoma (HCC), CYP39A1 protein and mRNA expression are downregulated compared to non-cancerous liver tissues. Overexpression of CYP39A1 inhibits HepG2 and SMMC-7721 cell viability, while knockout promotes HCC cell growth, indicating it may act as a tumor suppressor gene [1].

In exfoliation syndrome, carriers of functionally deficient CYP39A1 mutations have a significantly increased risk of glaucoma and blindness, and those with the CYP39A1 G204E mutation have a higher incidence of exfoliation glaucoma and more severe glaucoma [2,3].

In high-altitude pulmonary edema (HAPE), the methylation level of CYP39A1 is associated with the risk of HAPE in the Chinese population, with certain CpG sites having either a protective or risk-increasing role [4].

In advanced head and neck cancer, the CYP39A1 rs7761731 polymorphism is associated with a higher incidence of leucopenia and infections or death during intensive induction chemotherapy [5].

In cholangiocarcinoma, low CYP39A1 expression is correlated with metastasis and poor prognosis [6].

In conclusion, CYP39A1 plays diverse roles in multiple biological processes and disease conditions. Its downregulation in HCC, association with glaucoma in exfoliation syndrome, and link to HAPE risk, among others, highlight its significance. Gene knockout and related functional studies in various models contribute to understanding its role in these diseases, potentially providing new directions for disease diagnosis, prevention, and treatment [1-6].