Mouse Genome Informatics
ht
    Pkd1tm1Jzh/Pkd1+
either: (involves: 129S4/SvJae * C57BL/6) or (involves: 129S4/SvJae * BALB/c)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
digestive/alimentary system
• at >20 months, heterozygotes show multiple cystic structures lined by cuboidal cyst epithelium
• at >20 months, few acini are present; in areas of pancreatic lipomatosis, acini appear atrophic, isolated, and surrounded by mature adipocytes
• at >20 months, heterozygotes show dilatation of pancreatic ducts

endocrine/exocrine glands
• at >20 months, heterozygotes show multiple cystic structures lined by cuboidal cyst epithelium
• at >20 months, few acini are present; in areas of pancreatic lipomatosis, acini appear atrophic, isolated, and surrounded by mature adipocytes
• at >20 months, heterozygotes show dilatation of pancreatic ducts
• heterozygotes exhibit ductal plate malformation with occasional biliary microhamartomas
• at >20 months, few islets are present; in areas of pancreatic lipomatosis, islets appear isolated, and surrounded by mature adipocytes
• at >20 months, 10% of heterozygotes display macroscopic pancreatic cysts; no cysts are observed at 9-20 months
• some cysts with small lumens also contain cuboidal epithelium, with a large portion of eosinophilic cytoplasm suggesting an acinar origin
• at >20 months, pancreatic cystic lesions are surrounded by interstitial fibrosis
• at >20 months, the pancreas is massively replaced by adipose tissue

homeostasis/metabolism
N
• after 16 months, 7out of 8 heterozygotes exhibit normal serum creatinine levels (normal renal excretory function) relative to wild-type (J:52573)
• after 16 months, only 1 out of 8 heterozygotes exhibits severe disease and abnormal serum creatinine levels, indicating compromised renal excretory function

immune system
• in heterozygotes, impaired liver function correlates with cyst volume and cholangitis; increased cyst volume is due to increased secretion from the cystic epithelia
• in heterozygotes, large renal cysts are often surrounded by atrophic parenchyma with inflammation

liver/biliary system
• heterozygotes exhibit ductal plate malformation with occasional biliary microhamartomas
• in heterozygotes, impaired liver function correlates with cyst volume and cholangitis; increased cyst volume is due to increased secretion from the cystic epithelia
• heterozygotes with multiple liver cysts exhibit little residual parenchyma relative to wild-type mice
• at 9-14 months of age, 4 out of 15 heterozygotes (27%) display liver cysts; notably, no liver cysts are found in perinatal homozygotes
• after 14 months of age, 7 of 8 (87%) heterozygotes have liver cysts filled with clear or dark-brown fluid (up to 10 ml in volume) occupying one- to two-thirds of the liver
• most liver cysts are lined by cuboidal or squamous biliary-like epithelium positive for cytokeratin 19 (a biliary-specific epithelial marker) and show focal hyperplasia
• in heterozygotes, cyst number and impaired liver function are associated with a significant rise in ALT, AST and LDH enzyme levels with progressive age

renal/urinary system
N
• heterozygotes show no differences in kidney anatomy or histology up to 7 months of age; no renal cysts are observed at 220 days (J:43193)
• in heterozygotes, large renal cysts are often surrounded by atrophic parenchyma with inflammation
• in heterozygotes, large renal cysts are often surrounded by atrophic parenchyma with interstitial fibrosis
• at 9-14 months of age, heterozygotes with renal cysts show a greater than 5-fold dilatation in tubule diameter relative to wild-type
• at 9-14 months of age, 12 out of 15 heterozygotes (80%) display 1-7 renal cysts per mouse; 5 of these mutants show bilateral cysts
• after 16 months, 100% of heterozygotes have renal cysts (2-50 per mouse); 6 of 8 heterozygotes show bilateral cysts
• most cysts fail to stain with lotus tetragonolobus lectin, a proximal tubule marker, and dolichos biflorus agglutinin, a collecting tubule marker; in contrast, glomerular cysts are common
• notably, some cysts show loss of polycystin-1 expression; in addition, EGFR is improperly localized to apical membranes in cysts and some slightly dilated tubules
• in heterozygotes, large cysts contain epithelia that range from columnar to cuboidal to squamous

Mouse Models of Human Disease
OMIM IDRef(s)
Polycystic Kidney Disease 1; PKD1 173900 J:43193 , J:52573 , J:72627