The Novel Glis2 protein has critical roles in kidney development and renal failure

Abstract

Glis2 is a member of the GLI/ZIC/GLIS Krüppel-like zinc finger transcription factor family that contains five C2H2-type Krüppel-like zinc finger motifs. Glis2 is highly expressed in kidney and moderately in testis, lung, brain and ovary. During kidney development Glis2 is predominantly expressed in the ureteric bud, precursor of the collecting duct and ureteric bud cell lines also express high levels of Glis2 mRNA. To obtain insight into the physiological functions of Glis2, mice deficient in Glis2 expression were generated. Glis2−/− mice have a normal total body weight/size but have a significant smaller kidney. Furthermore, histopathological analysis of kidney sections demonstrated that Glis2 knockout mice develop nephropathy, degeneration of tubular epithelial cells and glomeruli throughout the cortex with multifocal lymphocytic and plasma cell infiltration. Nephropathy becomes more severe when mice age. Glis2−/− mice survival rate is dramatically decreased. The severity of the nephropathy is correlated with comparable increases in the level of creatinine and BUN values in serum. The degeneration of tubular epithelial cells may involve increased apoptosis. Our results suggest that the novel Krüppel-like zinc finger transcription factor, Glis2 exhibits critical roles in kidney development and progressive renal failure.