Defective epidermal growth factor gene expression in mice with polycystic kidney disease.
The C57BL/6J-cpk mouse has an inheritable form of polycystic kidney disease similar to the autosomal recessive disorder seen in humans. Between approximately 1 and 3 weeks of age, affected cpk mice develop numerous large cysts in the collecting tubule segment of kidney nephrons. The present study examined the ontogeny of renal and submandibular gland prepro-epidermal growth factor (preproEGF) gene expression in the cpk mouse using Northern blot hybridization and immunohistochemistry. There was a virtual absence of renal preproEGF gene expression in cystic kidneys over the 3-week postnatal period, during which time renal preproEGF mRNA and proEGF/EGF protein normally reach significant levels. PreproEGF mRNA was expressed in salivary glands of cystic mice; however, this mRNA could not be further elevated with testosterone suggesting that there are abnormalities in the regulation of the preproEGF gene in the submandibular gland, as well as in the kidney. Since renal preproEGF expression during the early postnatal period occurs when collecting duct cysts form, it is possible that a deficiency in renal proEGF or EGF contributes to the rapid development of collecting duct cysts and the concomitant renal failure in the C57BL/6J-cpk cystic mouse.
Gattone
V H
VH
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66103.
Andrews
G K
GK
Niu
F W
FW
Chadwick
L J
LJ
Klein
R M
RM
Calvet
J P
JP
D000818:Animals; D015152:Blotting, Northern; D004815:Epidermal Growth Factor / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D007690:Polycystic Kidney Diseases / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013363:Submandibular Gland / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000235:genetics
D011498:Protein Precursors; D012333:RNA, Messenger; D013739:Testosterone; D004815:Epidermal Growth Factor; D005723:gamma-Glutamyltransferase