Disruption of Gen1 Causes Congenital Anomalies of the Kidney and Urinary Tract in Mice.
Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common developmental defects in humans. Despite of several known CAKUT-related loci (HNF1B, PAX2, EYA1, etc.), the genetic etiology of CAKUT remains to be elucidated for most patients. In this study, we report that disruption of the Holliday Junction resolvase gene Gen1 leads to renal agenesis, duplex kidney, hydronephrosis, and vesicoureteral reflux (VUR) in mice. GEN1 interacts with SIX1 and enhances the transcriptional activity of SIX1/EYA1, a key regulatory complex of the GDNF morphogen. Gen1 mutation impairs Grem1 and Gdnf expression, resulting in excessive ureteric bud formation and defective ureteric bud branching during early kidney development. These results revealed an unidentified role of GEN1 in kidney development and suggested its contribution to CAKUT.
Duke Scholars
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Related Subject Headings
- Urinary Tract
- Protein Tyrosine Phosphatases
- Protein Binding
- Polymerase Chain Reaction
- Nuclear Proteins
- Mutation
- Mice
- Kidney
- Intracellular Signaling Peptides and Proteins
- In Situ Hybridization
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Urinary Tract
- Protein Tyrosine Phosphatases
- Protein Binding
- Polymerase Chain Reaction
- Nuclear Proteins
- Mutation
- Mice
- Kidney
- Intracellular Signaling Peptides and Proteins
- In Situ Hybridization