| First Author | Boisvert NC | Year | 2018 |
| Journal | Am J Physiol Renal Physiol | Volume | 315 |
| Issue | 2 | Pages | F353-F363 |
| PubMed ID | 29667913 | Mgi Jnum | J:281414 |
| Mgi Id | MGI:6367526 | Doi | 10.1152/ajprenal.00411.2017 |
| Citation | Boisvert NC, et al. (2018) Ubiquitin COOH-terminal hydrolase L1 deletion is associated with urinary alpha-klotho deficiency and perturbed phosphate homeostasis. Am J Physiol Renal Physiol 315(2):F353-F363 |
| abstractText | Loss of ubiquitin COOH-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme required for neuronal function, led to hyperphosphatemia accompanied by phosphaturia in mice, while calcium homeostasis remained intact. We therefore investigated the mechanisms underlying the phosphate imbalance in Uchl1(-/-) mice. Interestingly, phosphaturia was not a result of lower renal brush border membrane sodium-phosphate cotransporter expression as sodium-phosphate cotransporter 2a and 2c expression levels was similar to wild-type levels. Plasma parathyroid hormone and fibroblast growth factor 23 levels were not different; however, fibroblast growth factor 23 mRNA levels were significantly increased in femur homogenates from Uchl1(-/-) mice. Full-length and soluble alpha-klotho levels were comparable in kidneys from wild-type and Uchl1(-/-) mice; however, soluble alpha-klotho was reduced in Uchl1(-/-) mice urine. Consistent with unchanged components of 1,25(OH)2D3 metabolism (i.e., CYP27B1 and CYP24A1), sodium-phosphate cotransporter 2b protein levels were not different in ileum brush borders from Uchl1(-/-) mice, suggesting that the intestine is not the source of hyperphosphatemia. Nonetheless, when Uchl1(-/-) mice were fed a low-phosphate diet, plasma phosphate, urinary phosphate, and fractional excretion of phosphate were significantly attenuated and comparable to levels of low-phosphate diet-fed wild-type mice. Our findings demonstrate that Uchl1-deleted mice exhibit perturbed phosphate homeostasis, likely consequent to decreased urinary soluble alpha-klotho, which can be rescued with a low-phosphate diet. Uchl1(-/-) mice may provide a useful mouse model to study mild perturbations in phosphate homeostasis. |
