Polycystic kidney disease in SBM transgenic mice

Role of c-myc in disease induction and progression

M. Trudel, Laura Barisoni-Thomas, J. Lanoix, V. D'Agati

Research output: Contribution to journalArticle

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Abstract

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 ~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 ~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.

Original languageEnglish
Pages (from-to)219-229
Number of pages11
JournalAmerican Journal of Pathology
Volume152
Issue number1
StatePublished - Jan 1 1998
Externally publishedYes

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Polycystic Kidney Diseases
Transgenic Mice
Disease Progression
Kidney
Cysts
Newborn Animals
Phenotype
Autosomal Dominant Polycystic Kidney
Transgenes
Hyperplasia
In Situ Hybridization
Epithelium
Cell Proliferation
Apoptosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Polycystic kidney disease in SBM transgenic mice : Role of c-myc in disease induction and progression. / Trudel, M.; Barisoni-Thomas, Laura; Lanoix, J.; D'Agati, V.

In: American Journal of Pathology, Vol. 152, No. 1, 01.01.1998, p. 219-229.

Research output: Contribution to journalArticle

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