Mouse Genome Informatics
ht
    Pkd2tm1Som/Pkd2tm2Som
involves: 129/Sv * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• median survival time is 65 weeks compared to 94.1 weeks for wild-type

renal/urinary system
• in cystic renal epithelia cells, apoptotic indices are gradually increased from ~13.55% at 5-8 months of age to ~21.02% at 9-12-months of age, unlike in wild-type cells (~2.86%)
• at 5-8 months of age, ~2.86% nuclei of cystic renal epithelial cells are PCNA-positive relative to ~0.85% in wild-type cells; like in hepatic cysts, the % of PCNA-positive nuclei does not change significantly (~2.55%) with age
• mutant kidneys are enlarged with numerous macroscopically visible cysts
• at 5-8 months of age, mutant kidney weights represent ~2% of total body weight
• by 9-12 months of age, mutant kidney weights account for ~2.6% of total body weight
• all have bilateral renal cysts (J:47035)
• exhibit renal cyst formation by 6-10 weeks of age that progresses to cystic replacement of normal renal parenchyma later in life (J:59314)
• numerous macroscopically visible cysts are scattered on the kidney surface at an early disease stage (J:158354)
• total renal cystic volume decreases from ~ 40.67% of total kidney parenchyma at 5-8 months to ~31.04% at 9-12 months of age (J:158354)
• primary cilia in cystic renal epithelial cells remain normal despite a tendency to be shorter (J:158354)
• no significant fibrosis is noted around renal cysts in either age group (J:158354)

liver/biliary system
• cystic cholangiocytes lining intrahepatic bile ducts are enlarged with a thickened basement membrane and a significantly larger width (i.e. distance between two cell junctions) relative to wild-type cholangiocytes
• most cystic cholangiocytes are squamous in appearance
• cystic cholangiocyte cilia are ~2-fold shorter than wild-type
• ~25% of primary cilia in cystic cholangiocytes appear malformed (e.g. bulbs at the ciliary tip)
• at 5-8 months of age, mild fibrotic deposits are observed around liver cysts, occupying ~2.71% of total liver parenchyma relative to ~0.92% in wild-type controls
• no changes in hepatic fibrosis are found during disease progression
• mutant livers are significantly enlarged with multiple macroscopically visible cysts, often occupying most of the abdominal cavity
• at 5-8 months of age, mutant liver weights represent ~6% of total body weight relative to ~4.7% in wild-type controls
• by 9-12 months of age, mutant liver weights account for ~8% of total body weight, with no significant differences between male and female mice
• all have 1-10 liver cysts (J:47035)
• at 9-12 months of age, multiple fluid-filled cysts of different size and shapes are noted in the liver parenchyma (J:158354)
• hepatic cysts posses microvilli and have well-developed cellular junctions (J:158354)
• epithelial cells lining liver cysts stain positively for CK-19, suggesting that hepatic cysts arise from cholangiocytes (J:158354)
• most hepatic cysts are lined by a single layer of cholangiocytes while ~10% of liver cysts are multilayered (J:158354)
• total liver cystic volume increases from ~15.84% of total liver parenchyma at 5-8 months to ~23.26% at 9-12 months of age, as assessed by micro-CT scanning (J:158354)
• 3 of 6 have bile duct proliferation (J:47035)
• at 5-8 months of age, ~18.77% nuclei of cystic cholangiocytes are PCNA-positive relative to ~1.12% in wild-type cholangiocytes; however, the % of PCNA-positive nuclei does not change significantly with age (~20.26% at 9-12 months) (J:158354)
• at 5-8 months of age, apoptotic indices in cystic cholangiocytes are increased to ~3.41% relative to ~0.56% in wild-type cholangiocytes, but do not change significantly with age (~3.86% at 9-12 months)

homeostasis/metabolism
• develop azotemia/uremia
• at 5-8 months of age, mild fibrotic deposits are observed around liver cysts, occupying ~2.71% of total liver parenchyma relative to ~0.92% in wild-type controls
• no changes in hepatic fibrosis are found during disease progression

endocrine/exocrine glands
• cystic cholangiocytes lining intrahepatic bile ducts are enlarged with a thickened basement membrane and a significantly larger width (i.e. distance between two cell junctions) relative to wild-type cholangiocytes
• most cystic cholangiocytes are squamous in appearance
• cystic cholangiocyte cilia are ~2-fold shorter than wild-type
• ~25% of primary cilia in cystic cholangiocytes appear malformed (e.g. bulbs at the ciliary tip)
• 50% of mutants over 3 months of age have visible cysts

cellular
• cystic cholangiocyte cilia are ~2-fold shorter than wild-type
• ~25% of primary cilia in cystic cholangiocytes appear malformed (e.g. bulbs at the ciliary tip)
• in cystic renal epithelia cells, apoptotic indices are gradually increased from ~13.55% at 5-8 months of age to ~21.02% at 9-12-months of age, unlike in wild-type cells (~2.86%)
• at 5-8 months of age, ~2.86% nuclei of cystic renal epithelial cells are PCNA-positive relative to ~0.85% in wild-type cells; like in hepatic cysts, the % of PCNA-positive nuclei does not change significantly (~2.55%) with age

Mouse Models of Human Disease
OMIM IDRef(s)
Polycystic Kidney Disease 2; PKD2 613095 J:47035