Role of genetic modifiers in an orthologous rat model of ARPKD.
Physiol Genomics
; 44(15): 741-53, 2012 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-22669842
ABSTRACT
Human data and animal models of autosomal recessive polycystic kidney disease (ARPKD) suggest that genetic factors modulate the onset and severity of the disease. We report here for the first time that ARPKD susceptibility is attenuated by introgressing the mutated Pkhd1 disease allele from the polycystic kidney (PCK) rat onto the FHH (Fawn-Hooded Hypertensive) genetic background. Compared with PCK, the FHH.Pkhd1 strain had significantly decreased renal cyst formation that coincided with a threefold reduction in mean kidney weights. Further analysis revealed that the FHH. Pkhd1 is protected from increased blood pressure as well as elevated plasma creatinine and blood urea nitrogen levels. On the other hand, liver weight and biliary cystogenesis revealed no differences between PCK and FHH.Pkdh1, indicating that genes within the FHH genetic background prevent the development of renal, but not hepatic, manifestations of ARPKD. Microarray expression analysis of kidneys from 30-day-old PCK rats revealed increased expression of genes previously identified in PKD renal expression profiles, such as inflammatory response, extracellular matrix synthesis, and cell proliferation genes among others, whereas the FHH.Pkhd1 did not show activation of these common markers of disease. This newly developed strain can serve as a tool to map modifier genes for renal disease in ARPKD and provides further insight into disease variability and pathophysiology.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Rim Policístico Autossômico Recessivo
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Modelos Animais de Doenças
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Genes Modificadores
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Physiol Genomics
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos