RGD Reference Report - A mouse model of autosomal recessive polycystic kidney disease with biliary duct and proximal tubule dilatation. - Rat Genome Database

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A mouse model of autosomal recessive polycystic kidney disease with biliary duct and proximal tubule dilatation.

Authors: Woollard, J R  Punyashtiti, R  Richardson, S  Masyuk, T V  Whelan, S  Huang, B Q  Lager, D J  vanDeursen, J  Torres, V E  Gattone, V H  LaRusso, N F  Harris, P C  Ward, C J 
Citation: Woollard JR, etal., Kidney Int. 2007 Aug;72(3):328-36. doi: 10.1038/sj.ki.5002294. Epub 2007 May 23.
RGD ID: 14700917
Pubmed: PMID:17519956   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.ki.5002294   (Journal Full-text)

Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the polycystic kidney and hepatic disease (PKHD1) gene encoding the protein fibrocystin/polyductin. The aim of our study was to produce a mouse model of ARPKD in which there was no functional fibrocystin/polyductin to study the pathophysiology of cystic and fibrocystic disease in renal and non-renal tissues. Exon 2 of the gene was deleted and replaced with a neomycin resistance cassette flanked by loxP sites, which could be subsequently removed by Cre-lox recombinase. Homozygous Pkhd1(del2/del2) mice were viable, fertile and exhibited hepatic, pancreatic, and renal abnormalities. The biliary phenotype displayed progressive bile duct dilatation, resulting in grossly cystic and fibrotic livers in all animals. The primary cilia in the bile ducts of these mutant mice had structural abnormalities and were significantly shorter than those of wild-type (WT) animals. The Pkhd1(del2/del2) mice often developed pancreatic cysts and some exhibited gross pancreatic enlargement. In the kidneys of affected female mice, there was tubular dilatation of the S3 segment of the proximal tubule (PT) starting at about 9 months of age, whereas male mice had normal kidneys up to 18 months of age. Inbreeding the mutation onto BALBc/J or C57BL/6J background mice resulted in females developing PT dilatation by 3 months of age. These inbred mice will be useful resources for studying the mechanisms underlying the pathogenesis of ARPKD.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PKHD1Humanautosomal recessive polycystic kidney disease  ISOPkhd1 (Mus musculus)DNA:deletion:exon:RGD 
Pkhd1Ratautosomal recessive polycystic kidney disease  ISOPkhd1 (Mus musculus)DNA:deletion:exon:RGD 
Pkhd1Mouseautosomal recessive polycystic kidney disease  IMP DNA:deletion:exon:RGD 
PKHD1Humanliver cirrhosis  ISOPkhd1 (Mus musculus)DNA:deletion:exon:RGD 
Pkhd1Ratliver cirrhosis  ISOPkhd1 (Mus musculus)DNA:deletion:exon:RGD 
Pkhd1Mouseliver cirrhosis  IMP DNA:deletion:exon:RGD 
PKHD1HumanPancreatic Cyst  ISOPkhd1 (Mus musculus)DNA:deletion:exon:RGD 
Pkhd1RatPancreatic Cyst  ISOPkhd1 (Mus musculus)DNA:deletion:exon:RGD 
Pkhd1MousePancreatic Cyst  IMP DNA:deletion:exon:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pkhd1  (PKHD1 ciliary IPT domain containing fibrocystin/polyductin)

Genes (Mus musculus)
Pkhd1  (polycystic kidney and hepatic disease 1)

Genes (Homo sapiens)
PKHD1  (PKHD1 ciliary IPT domain containing fibrocystin/polyductin)


Additional Information