Laboratory Investigation

Kidney International (1996) 50, 453–461; doi:10.1038/ki.1996.336

Expression of a cut-related homeobox gene in developing and polycystic mouse kidney

Gregory B Vanden Heuvel, Rolf Bodmer, Kevin R McConnell, Glenn T Nagami and Peter Igarashi

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; Department of Biology, University of Michigan Ann Arbor, Michigan; and Medical and Research Services, West Los Angeles Veterans Affairs Medical Center, Los Angeles, California, USA

Correspondence: Peter Igarashi MD, Section of Nephrology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520-8029, USA. E-mail: peter.igarashi@yale.edu

Received 16 January 1996; Revised 1 March 1996; Accepted 4 March 1996.

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Abstract

Expression of a cut-related homeobox gene in developing and polycystic mouse kidney. cut is a diverged homeobox gene that is essential for normal development of the Malpighian tubules in Drosophila melanogaster. Homologues of Drosophila cut that encode transcriptional repressors have been identified in several mammalian species and cell lineages. We examined the expression of a murine cut homologue (named Cux-1) in the developing mouse using Northern blot analysis and in situ hybridization. At 12.5 d.p.c. and 13.5 d.p.c, Cux-1 was highly expressed in a subset of embryonic tissues, including the developing metanephros. Within the metanephros, Cux-1 was expressed in the nephrogenic zone including both mesenchymal cells (uninduced and condensed mesenchyme) and epithelial cells (ureteric buds, renal vesicles, S-shaped bodies). During later stages of nephrogenesis, Cux-1 was down-regulated such that there was minimal expression in mature glomeruli and tubules. In addition, Cux-1 was detected in the mesonephros, mesonephric duct, and bladder. Expression of Cux-1 was also examined in polycystic kidneys from C57BL/6J-cpk/ cpk mice. At 21 days of age, Cux-1 was highly expressed in cyst epithelium of polycystic kidneys but was minimally expressed in kidneys from phenotypically normal littermates. These results demonstrate that a cut-related homeobox gene is expressed in the developing kidney and urinary tract of the mouse. Expression of Cux-1 in the kidney is inversely related to degree of cellular differentiation. Cux-1 may encode a transcriptional repressor that inhibits terminally differentiated gene expression during early stages of nephrogenesis.

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