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Impaired kidney function and anatomy in dietarily‐rescued calcineurin (alpha isoform) knockout mice
Author(s) -
Gooch Jennifer L,
Ecelbarger Carolyn,
Reddy Ramesh N,
Tsukerman Susanna,
Madsen Kirsten
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.868.19
Subject(s) - endocrinology , medicine , aldosterone , calcineurin , knockout mouse , nephron , epithelial sodium channel , kidney , distal convoluted tubule , gene isoform , renal function , podocyte , chemistry , biology , sodium , transplantation , receptor , proteinuria , biochemistry , organic chemistry , gene
Previously, we identified a predominant role for the alpha isoform of calcineurin (CnAα) in normal kidney development and function. However, many experiments were limited by failure to thrive and early lethality of CnAα knockout mice. Recently, we reported the rescue of CnAα −/− mice by dietary compensation for defective salivary enzyme secretion. We now provide the first report of kidney anatomy and function in adult knockout mice. The data show that despite comparable body mass, kidney size is reduced and GFR is lower in null mice. In additional, although total glomerular number is unchanged, a significant proportion of glomeruli are abnormal. Examination of the protein expression of major renal sodium transporters, channels, and exchangers reveals modest changes in proximal tubule transporters, but substantial (40–60%) decreases in the aldosterone‐sensitive Na‐Cl cotransporter (NCC), the α‐subunit of the epithelial sodium channel (ENaC), and the 70‐Da band of γ‐ENaC. Null mice also show decreased urinary potassium and hyperkalemia suggesting impaired collecting duct function. These findings are consistent with clinical observations of aldosterone resistance with use of calcineurin inhibitors and provide new experimental evidence that, in addition to glomerular development, CnAα plays a role in sodium and potassium handling by the distal nephron.