Background:

Janus kinase 3 (JAK3) is a tyrosine kinase which is implicated in interleukin signaling. In men, JAK3 deficiency causes the severe combined immunodeficiency (SCID) syndrome. Apart from hematopoetic cells, it is expressed in the kidney where its exact role is unknown. Here, we tested whether JAK3 influences renal phosphate handling.

Methods:

The renal phosphate carrier Napi-IIa was heterologously expressed in Xenopus oocytes with and without JAK3. Napi-IIa activity was estimated from the phosphate-induced current using the Two-electrode-voltage clamp. In addition, gene-targeted mice deficient for JAK3 (jak3-/-) were compared to wild type mice (jak3+/+). Mice were analyzed in metabolic cages, and urinary and serum phosphate, calcium and serum FGF23, PTH and calcitriol were determined.

Results:

In vitro, the phosphate-induced current in NapiII-expressing Xenopus oocytes was significantly enhanced by coexpression of Jak3. In vivo, compared to jak3+/+ mice jak3-/- mice showed phosphaturia. Serum phosphate level was not different between jak3+/+ and jak3-/- mice. The serum concentration of FGF23 was significantly higher in jak3-/- mice than in jak3+/+ mice. PTH serum concentration did not differ in jak3+/+ and jak3-/- mice, but calcitriol concentration was significantly elevated in jak3-/- compared to jak3+/+ mice. Hence, renal calcium excretion tended to be lower and serum calcium concentration to be higher in jak3-/- mice compared to jak3+/+ mice.

Conclusions:

JAK3 regulates both, the release of FGF23 and the renal phosphate transporter Napi-IIa thereby controlling renal phosphate excretion.