RGD Reference Report - Polycystic kidney disease in SBM transgenic mice: role of c-myc in disease induction and progression. - Rat Genome Database

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Polycystic kidney disease in SBM transgenic mice: role of c-myc in disease induction and progression.

Authors: Trudel, M  Barisoni, L  Lanoix, J  D'Agati, V 
Citation: Trudel M, etal., Am J Pathol. 1998 Jan;152(1):219-29.
RGD ID: 7207451
Pubmed: PMID:9422539   (View Abstract at PubMed)
PMCID: PMC1858107   (View Article at PubMed Central)

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 approximately 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 approximately 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.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
MYCHumanpolycystic kidney disease  ISOMyc (Mus musculus) RGD 
MycRatpolycystic kidney disease  ISOMyc (Mus musculus) RGD 
MycMousepolycystic kidney disease  IMP  RGD 


Genes (Rattus norvegicus)
Myc  (MYC proto-oncogene, bHLH transcription factor)

Genes (Mus musculus)
Myc  (myelocytomatosis oncogene)

Genes (Homo sapiens)
MYC  (MYC proto-oncogene, bHLH transcription factor)