| First Author | Singh A | Year | 2019 |
| Journal | Aging Cell | Volume | 18 |
| Issue | 3 | Pages | e12949 |
| PubMed ID | 30920112 | Mgi Jnum | J:295400 |
| Mgi Id | MGI:6460477 | Doi | 10.1111/acel.12949 |
| Citation | Singh A, et al. (2019) Noncoding variations in Cyp24a1 gene are associated with Klotho-mediated aging phenotypes in different strains of mice. Aging Cell 18(3):e12949 |
| abstractText | In mutant mice, reduced levels of Klotho promoted high levels of active vitamin D in the serum. Genetic or dietary manipulations that diminished active vitamin D alleviated aging-related phenotypes caused by Klotho down-regulation. The hypomorphic Klotho [kl/kl] allele that decreases Klotho expression in C3H, BALB/c, 129, and C57BL/6 genetic backgrounds substantially increases 1,25(OH)2D3 levels in the sera of susceptible C3H, BALB/c, and 129, but not C57BL/6 mice. This may be attributed to increased basal expression of Cyp24a1 in C57BL/6 mice, which promotes inactivation of 1,25(OH)2D3. Decreased expression of Cyp24a1 in susceptible strains was associated with genetic alterations in noncoding regions of Cyp24a1 gene, which were strongly reminiscent of super-enhancers that regulate gene expression. These observations suggest that higher basal expression of an enzyme required for catabolizing vitamin D renders B6-kl/kl mice less susceptible to changes in Klotho expression, providing a plausible explanation for the lack of aging phenotypes on C57BL/6 strain. |
