Distinct patterns of kidney and liver cyst growth in pkd2(WS25/-) mice.
BACKGROUND
Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease that results in the development of cystic kidneys and liver. Pkd2(WS25/-) mice are a key genetic mouse model of human ADPKD that recapitulate the 'molecular recessive' nature of human ADPKD. Providing the foundation for future long-term studies, the present work documents distinct patterns of long-term cyst growth in the kidneys and liver of male and female pkd2(WS25/-) mice.


METHODS
Gravimetric measurements documented the progression of kidney and liver growth in male and female pkd2(WS25/-) mice over 12 months. A fast imaging with steady-state precision-magnetic resonance imaging (FISP-MRI) technique to measure kidney and liver organ and cyst volumes was optimized and validated. Longitudinal FISP-MRI analyses of changes in cyst volumes were performed in pkd2(WS25/-) mice over 15 months.


RESULTS
Male and female pkd2(WS25/-) mice had significant increases in kidney weights after 4 months of age. The progression of kidney growth was minimal after 4 months of age. Liver cyst growth in male pkd2(WS25/-) mice was minimal after 4 months of age but showed an accelerated rate of growth after 8 months of age. Female pkd2(WS25/-) mice also showed accelerated growth but this was delayed in time when compared with male pkd2(WS25/-) mice.


CONCLUSIONS
Pkd2(WS25/-) mice are a genetic mouse model that recapitulates the early phenotypic characteristics of human ADPKD kidney cystogenesis. Male pkd2(WS25/-) mice consistently display a late progression in liver growth that is seen in clinically impacted livers of human ADPKD patients.
Doctor
R Brian
RB
Department of Medicine, University of Colorado Denver, Aurora, CO, USA. brian.doctor@ucdenver.edu
Serkova
Natalie J
NJ
Hasebroock
Kendra M
KM
Zafar
Iram
I
Edelstein
Charles L
CL
D000818:Animals; D003560:Cysts / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D007089:Image Enhancement; D007668:Kidney / Q000473:pathology*; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016891:Polycystic Kidney, Autosomal Dominant / Q000473:pathology*; D050396:TRPP Cation Channels / Q000235:genetics*
D050396:TRPP Cation Channels
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