Calcineurin A-α but not A-β is required for normal kidney development and function

Jennifer L. Gooch, Juan J. Toro, Rebecca L. Guler, Jeffrey L. Barnes

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Calcineurin is an important signaling molecule in the kidney and may be involved in a variety of processes. The phosphatase subunit of calcineurin (CnA) has three isoforms, α, β, and γ. In this study, we investigated the effect of loss of calcineurin A-α (CnA-α) or calcineurin A-β (CnA-β) on the development and function of the kidney. Total calcineurin expression and activity was significantly reduced in whole kidney homogenates from both CnA-α -/- and CnA-β -/- mice. Kidneys of CnA-β -/- mice appear normal and the mice develop with no phenotypic abnormalities. In contrast, kidneys of CnA-α -/- animals fail to fully develop. In particular, postnatal maturation of the nephrogenic zone (NZ) is defective. Within the NZ, glomeruli also fail to mature and lack mesangial cells. In addition to alterations in development, there is an absence of proliferation and an increase of cell death in the NZ with loss of CnA-α. Finally, increased collagen deposition is observed and serum creatinine levels are significantly increased in CnA-α -/- animals compared to wild-type littermates, indicating that kidney function is impaired. In summary, absence of CnA-α but not CnA-β leads to a defect in normal maturation of the NZ and glomeruli, alterations in the cell cycle, and impaired kidney function.

Original languageEnglish (US)
Pages (from-to)1755-1765
Number of pages11
JournalAmerican Journal of Pathology
Volume165
Issue number5
DOIs
StatePublished - Nov 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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