title: Epidermal growth factor receptor activity mediates renal cyst formation in polycystic kidney disease.
abstract: A consistent phenotype observed in both human patients and several different mouse models of autosomal recessive polycystic kidney disease (ARPKD) is an increased activity of the epidermal growth factor receptor (EGFR) in the affected kidneys. To determine whether this increased activity of the EGFR is a functional event that is directly part of the disease pathway of renal cyst formation, we used a genetic approach to introduce a mutant EGFR with decreased tyrosine kinase activity into a murine model of ARPKD. We found that the modified form of the EGFR could block the increase in EGFR-specific tyrosine kinase activity that normally accompanies the development of renal cysts, and this correlated with an improvement in kidney function and a substantial decrease in cyst formation in the collecting ducts. These results suggest that changes in the expression of the EGFR contribute to the formation of cysts in the collecting ducts, and that drugs that target the tyrosine kinase activity of the EGFR may potentially be therapeutic in ARPKD.
authors.affiliation: Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Richards
authors.forename: W E
authors.initials: WE
authors.lastname: Sweeney
authors.forename: B K
authors.initials: BK
authors.lastname: Yoder
authors.forename: J E
authors.initials: JE
authors.lastname: Wilkinson
authors.forename: R P
authors.initials: RP
authors.lastname: Woychik
authors.forename: E D
authors.initials: ED
authors.lastname: Avner
mesh_terms: D000818:Animals; D015153:Blotting, Western; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D007690:Polycystic Kidney Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism
chemical_list: D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases