| First Author | Trudel M | Year | 1998 |
| Journal | Am J Pathol | Volume | 152 |
| Issue | 1 | Pages | 219-29 |
| PubMed ID | 9422539 | Mgi Jnum | J:45203 |
| Mgi Id | MGI:1194542 | Citation | Trudel M, et al. (1998) Polycystic kidney disease in SBM transgenic mice: role of c-myc in disease induction and progression. Am J Pathol 152(1):219-29 |
| abstractText | SBM mouse is a unique transgenic model of polycystic kidney disease (PKD) produced by dysregulation of c-myc in the kidneys, Our previous demonstration that c-myc is overexpressed in human autosomal polycystic kidney disease (ADPKD) prompted us to investigate the pathogenetic role of c-myc in the induction and progression of the cystogenic phenotype in our mouse model, In young SBM kidneys, c-myc was two- to threefold increased with persistent expression levels into adulthood, an age when c- myc is normally undetectable. In situ hybridization analysis of the c-myc transgene demonstrated intense signal specifically overlying glomerular and tubular epithelium of developing cysts in fetal and young kidneys. Increased expression of c-myc correlated with the initiation and progression of the PKD phenotype as evidenced by early tubular and glomerular cysts at E16.5. Cyst number and size increased with age, with co- development of glomerular and tubular epithelial hyperplasia, Consistently, the mean renal proliferative index was increased similar to 5- to 20-fold in noncystic and cystic tubules of newborn SBM animals compared with littermate controls. Similarly, in fetal and newborn kidneys the tubular apoptotic indices were increased similar to three- to ninefold over controls. Both proliferation and apoptotic rates in cystic tubules approached levels in developing tubules from the normal nephrogenic zone. We conclude that the pathogenesis of PKD hinges on a critical imbalance in c-myc regulation of the opposing processes of cell proliferation and apoptosis, recapitulating the cellular phenomena in developing fetal kidney. |
