TY - JOUR
T1 - Renal function of gene-targeted mice lacking both SGK1 and SGK3
AU - Grahammer, Florian
AU - Artunc, Ferruh
AU - Sandulache, Diana
AU - Rexhepaj, Rexhep
AU - Friedrich, Björn
AU - Risler, Teut
AU - McCormick, James A.
AU - Dawson, Kevin
AU - Wang, Jian
AU - Pearce, David
AU - Wulff, Peer
AU - Kuhl, Dietmar
AU - Lang, Florian
PY - 2006/4
Y1 - 2006/4
N2 - Serum- and glucocorticoid-inducible kinase (SGK) 1 and SGK3 share the ability to upregulate several ion channels, including the epithelial Na + channel. Whereas SGK1 is under genomic control of mineralocorticoids and glucocorticoids, SGK3 is constitutively expressed. The SKG1-knockout (sgk1-/-) mouse is seemingly normal when it is fed a standard diet, but its ability to retain NaCl is impaired when it is fed a salt-deficient diet. In the SGK3-knockout (sgk3-/-) mouse fed standard and salt-deficient diets, hair growth is strikingly delayed but NaCl excretion is normal. Thus the possibility was considered that SGK1 and SGK3 could mutually replace each other, thus preventing severe NaCl loss in sgk1 -/- and sgk3-/- mice. We crossed SGK1- and SGK3-knockout mice and compared renal electrolyte excretion of the double mutants (sgk1 -/-/sgk3-/-) with that of their wildtype littermates (sgk1+/+/sgk3+/+). Similar to sgk3-/- mice, the sgk1-/-/sgk3-/- mice display delayed hair growth. Blood pressure was slightly, but significantly (P < 0.03), lower in sgk1 -/-/sgk3-/- (102 ± 4 mmHg) than in sgk1 +/+/sgk3+/+ (114 ± 3 mmHg) mice, a difference that was maintained in mice fed low- and high-salt diets. Plasma aldosterone concentrations were significantly (P < 0.01) higher in sgk1 -/-/sgk3-/- than in sgk1+/+sgk3+/+ mice fed control (511 ± 143 vs. 143 ± 32 pg/ml) and low-salt (1,325 ± 199 vs. 362 ± 145 pg/ml) diets. During salt depletion, absolute and fractional excretions of Na+ were significantly (P < 0.01) higher in sgk1-/-/sgk3-/- (1.2 ± 0.2 μmol/24 h g body wt, 0.12 ± 0.03%) than in sgk1+/+/ sgk3+/+ (0.4 ± 0.1 μmol/24 h g body wt, 0.04 ± 0.01%) mice. The sgk1-/-/sgk3-/- mice share the delayed hair growth with sgk3-/- mice and the modestly impaired renal salt retention with sgk1-/- mice. Additional lack of the isoform kinase does not substantially compound the phenotype for either property.
AB - Serum- and glucocorticoid-inducible kinase (SGK) 1 and SGK3 share the ability to upregulate several ion channels, including the epithelial Na + channel. Whereas SGK1 is under genomic control of mineralocorticoids and glucocorticoids, SGK3 is constitutively expressed. The SKG1-knockout (sgk1-/-) mouse is seemingly normal when it is fed a standard diet, but its ability to retain NaCl is impaired when it is fed a salt-deficient diet. In the SGK3-knockout (sgk3-/-) mouse fed standard and salt-deficient diets, hair growth is strikingly delayed but NaCl excretion is normal. Thus the possibility was considered that SGK1 and SGK3 could mutually replace each other, thus preventing severe NaCl loss in sgk1 -/- and sgk3-/- mice. We crossed SGK1- and SGK3-knockout mice and compared renal electrolyte excretion of the double mutants (sgk1 -/-/sgk3-/-) with that of their wildtype littermates (sgk1+/+/sgk3+/+). Similar to sgk3-/- mice, the sgk1-/-/sgk3-/- mice display delayed hair growth. Blood pressure was slightly, but significantly (P < 0.03), lower in sgk1 -/-/sgk3-/- (102 ± 4 mmHg) than in sgk1 +/+/sgk3+/+ (114 ± 3 mmHg) mice, a difference that was maintained in mice fed low- and high-salt diets. Plasma aldosterone concentrations were significantly (P < 0.01) higher in sgk1 -/-/sgk3-/- than in sgk1+/+sgk3+/+ mice fed control (511 ± 143 vs. 143 ± 32 pg/ml) and low-salt (1,325 ± 199 vs. 362 ± 145 pg/ml) diets. During salt depletion, absolute and fractional excretions of Na+ were significantly (P < 0.01) higher in sgk1-/-/sgk3-/- (1.2 ± 0.2 μmol/24 h g body wt, 0.12 ± 0.03%) than in sgk1+/+/ sgk3+/+ (0.4 ± 0.1 μmol/24 h g body wt, 0.04 ± 0.01%) mice. The sgk1-/-/sgk3-/- mice share the delayed hair growth with sgk3-/- mice and the modestly impaired renal salt retention with sgk1-/- mice. Additional lack of the isoform kinase does not substantially compound the phenotype for either property.
KW - Aldosterone
KW - Blood pressure
KW - Epithelial sodium channel
KW - Kidney
KW - Mineralocorticoids
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U2 - 10.1152/ajpregu.00484.2005
DO - 10.1152/ajpregu.00484.2005
M3 - Article
C2 - 16537821
AN - SCOPUS:33646481343
SN - 0363-6119
VL - 290
SP - R945-R950
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 4
ER -