1. Volume 87, Issue 4, Pages 728-737 (April 2015)
Janus kinase 3 regulates renal 25-hydroxyvitamin D 1α-hydroxylase expression, calcitriol formation, and phosphate metabolism 
Anja T. Umbach, Bingbing Zhang, Christoph Daniel, Abul Fajol, Ana Velic, Zohreh Hosseinzadeh, Shefalee K. Bhavsar, C. Thomas Bock, Reinhard Kandolf, Bernd J. Pichler, Kerstin U. Amann, Michael Föller, Florian Lang 
Kidney International 
Volume 87, Issue 4, Pages (April 2015)
DOI: /ki
Copyright © 2015 International Society of Nephrology Terms and Conditions

2. Figure 1
25-hydroxyvitamin D 1α-hydroxylase expression and 1,25(OH)2D3 serum levels were enhanced in jak3‒/‒ mice. (a) Arithmetic mean±s.e.m. (n=13–18/group) of the relative Cyp27b1 (25-hydroxyvitamin D 1α-hydroxylase) level in renal tissue from Janus kinase 3 (JAK3)-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). (b) Arithmetic mean±s.e.m. (n=18–20/group) of the serum 1,25(OH)2 D3 level in JAK3-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). (c) Morphological evaluation of the kidneys. Glomerular changes were graded by the glomerular sclerosis score (GSI) (upper left diagram) and tubular changes by the tubular injury score (TSI) (upper right diagram) using periodic acid-Schiff-stained renal sections. Representative microphotographs of glomeruli showing strong glomerulosclerosis in jak3+/+ mice (lower left panel) but not in jak3‒/‒ mice (lower right panel). *P<0.05 indicates significant difference from jak3+/+ mice (U-test).
Kidney International  , DOI: ( /ki )
Copyright © 2015 International Society of Nephrology Terms and Conditions

3. Figure 2
IL-12 serum levels were higher and transcription factor IRF-1 was more abundant in kidneys from jak3‒/‒ mice. (a) Arithmetic mean±s.e.m. (n=10–11/group) of the serum IL-12 concentration in Janus kinase 3 (JAK3)-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). (b) Arithmetic mean±s.e.m. (n=22–24/group) of the relative interferon regulatory factor-1 (IRF-1) transcript level in renal tissue from JAK3-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). (c) Immunohistochemical images of kidneys from JAK3-deficient mice (jak3‒/‒) and wild-type mice (jak3+/+). Staining of IRF-1 is in brown. (d and e) Colocalization of IRF-1 and 25-hydroxyvitamin D 1α-hydroxylase in jak3+/+ and jak3‒/‒ mice. Renal biopsies were subjected to immunohistologic double staining for 25-hydroxyvitamin D 1α-hydroxylase (1αH, red staining) and IRF-1 (brown nuclear staining). Representative pictures from the renal cortex (upper panels) and renal papilla (lower panels) from jak3+/+ mice (left panels) and jak3‒/‒ mice (right panels) are shown. The scale bars represent a distance of 50μm. The number of IRF-1-positive cells, as assessed by immunohistochemistry, was evaluated in renal sections for both genotypes (e). (f) Arithmetic mean±s.e.m. (n=7–8/group) of plasma parathyroid hormone (PTH) levels in JAK3-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). *P<0.05, and **P<0.01 indicate significant difference from jak3+/+ mice (U-test).
Kidney International  , DOI: ( /ki )
Copyright © 2015 International Society of Nephrology Terms and Conditions

4. Figure 3
Serum C-terminal FGF23 concentration was elevated in jak3‒/‒ compared with jak3+/+ mice. (a) Arithmetic mean±s.e.m. (n=20–21/group) of the serum FGF23 level in Janus kinase 3 (JAK3)-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). (b) Original western blot showing the renal protein abundance of Klotho and GAPDH in JAK3-deficient mice (‒/‒) and in wild-type mice (+/+). (c) Arithmetic mean±s.e.m. (n=11/group) of the Klotho/GAPDH expression ratio in JAK3-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). ***P<0.001 indicates significant difference from jak3+/+ mice (t-test).
Kidney International  , DOI: ( /ki )
Copyright © 2015 International Society of Nephrology Terms and Conditions

5. Figure 4
Fecal phosphate excretion was reduced in jak3‒/‒ mice. (a) Arithmetic mean±s.e.m. (n=15–16/group) of food intake in Janus kinase 3 (JAK3)-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). (b) Arithmetic mean±s.e.m. (n=6/group) of fecal dry weight in JAK3-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). (c) Arithmetic mean±s.e.m. (n=11–12/group) of fecal phosphate excretion in JAK3-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). ***P<0.001 indicates significant difference from jak3+/+ mice (t-test).
Kidney International  , DOI: ( /ki )
Copyright © 2015 International Society of Nephrology Terms and Conditions

6. Figure 5
Renal phosphate excretion was enhanced in jak3‒/‒ mice. (a) Arithmetic mean±s.e.m. (n=15–16/group) of the serum phosphate concentration in Janus kinase 3 (JAK3)-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). (b) Arithmetic mean±s.e.m. of renal phosphate excretion (n=15–16/group; left panel) and fractional renal phosphate excretion (n=13–15/group; right panel) in JAK3-deficient mice (jak3‒/‒, black bars) and wild-type mice (jak3+/+, white bars). (c) Arithmetic mean±s.e.m. (n=13–14/group) of the serum Ca2+ concentration in JAK3-deficient mice (jak3‒/‒, black bar) and wild-type mice (jak3+/+, white bar). (d) Arithmetic mean±s.e.m. of renal Ca2+ excretion (n=15–16/group; left panel) and fractional Ca2+ excretion (n=13–14/group; right panel) in JAK3-deficient mice (jak3‒/‒, black bars) and wild-type mice (jak3+/+, white bars). ***P<0.001 indicates significant difference from jak3+/+ mice (Student’s t-test).
Kidney International  , DOI: ( /ki )
Copyright © 2015 International Society of Nephrology Terms and Conditions

7. Figure 6
JAK3 enhanced the phosphate-induced current in Napi-IIa-expressing Xenopus oocytes. (a) Arithmetic mean±s.e.m. (n=10–16) of phosphate (2mM)-induced current in Xenopus oocytes injected with water (first bar) or expressing Napi-IIa without (second bar) or with Janus kinase 3 (JAK3; third bar) or with inactive JAK3K851A (fourth bar). *P<0.05 indicates significant difference from oocytes expressing only Napi-IIa (analysis of variance (ANOVA)). ###P<0.001 indicates significant difference between oocytes expressing JAK3 and oocytes expressing JAK3K851A (ANOVA). (b) JAK3 and GAPDH mRNA expression analysis in the indicated tissues from jak3+/+ and jak3‒/‒ mice.
Kidney International  , DOI: ( /ki )
Copyright © 2015 International Society of Nephrology Terms and Conditions

8. Figure 7
Tentative model illustrating direct and indirect influences of JAK3 deficiency on renal phosphate excretion. 1,25(OH)2D3, calcitriol; 1αH, 25-hydroxyvitamin D 1α-hydroxylase; FGF23, fibroblast growth factor 23; GSK3ß, glycogen synthase kinase 3ß; IL-12, interleukin 12; IRF-1, interferon regulatory factor-1; Pi, inorganic phosphate; PI3K, phosphoinositide 3 kinase; PKB/Akt, protein kinase B.
Kidney International  , DOI: ( /ki )
Copyright © 2015 International Society of Nephrology Terms and Conditions