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Defective epidermal growth factor gene expression in mice with polycystic kidney disease
V H Gattone1, G K Andrews, F W Niu
1Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66103.
Abstract:
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.
Insights
Polycystic kidney disease in C57BL/6J-cpk mice is linked to a lack of renal prepro-epidermal growth factor (preproEGF) gene expression. This deficiency may contribute to cyst formation and kidney failure in affected mice.
Area of Science:
- Nephrology
- Genetics
- Developmental Biology
Background:
- The C57BL/6J-cpk mouse model exhibits an inherited polycystic kidney disease (PKD) mirroring human autosomal recessive PKD.
- Affected mice develop renal cysts in collecting tubules between 1 and 3 weeks of age, leading to renal failure.
Purpose of the Study:
- To investigate the ontogeny of renal and submandibular gland prepro-epidermal growth factor (preproEGF) gene expression in the C57BL/6J-cpk mouse model of PKD.
- To determine the potential role of preproEGF deficiency in the development of renal cysts and kidney failure.
Main Methods:
- Northern blot hybridization was employed to analyze preproEGF mRNA levels in kidneys and submandibular glands.
- Immunohistochemistry was used to assess proEGF/EGF protein expression in affected tissues.
Main Results:
- A significant absence of renal preproEGF gene expression was observed in cystic kidneys during the critical 1-3 week postnatal period.
- While preproEGF mRNA was present in the salivary glands of cystic mice, it showed impaired inducibility by testosterone, suggesting dysregulation.
- Normal renal preproEGF mRNA and proEGF/EGF protein levels are typically achieved during this developmental window.
Conclusions:
- A deficiency in renal preproEGF expression during early postnatal development may be a critical factor in the rapid formation of collecting duct cysts.
- The findings suggest that impaired renal proEGF or EGF contributes to the pathogenesis of PKD and renal failure in C57BL/6J-cpk mice.
- Abnormalities in preproEGF gene regulation were identified in both the kidney and submandibular gland of these mice.