Analysis Tools
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
|
|
• acini appear atrophic in areas of pancreatic lipomatosis
|
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
|
|
• acini appear atrophic in areas of pancreatic lipomatosis
|
|
• heterozygotes exhibit ductal plate malformation with occasional biliary microhamartomas
|
|
• at >20 months, few islets are present
|
pancreas cyst
(
J:72627
)
|
• 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
|
|
• 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
|
liver cyst
(
J:52573
)
|
• 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, 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
|
|
• 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
|
kidney cyst
(
J:52573
)
|
• 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
|
|
• 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
|
growth/size/body
pancreas cyst
(
J:72627
)
|
• 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
|
kidney cyst
(
J:52573
)
|
• 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
|
liver cyst
(
J:52573
)
|
• 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
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| polycystic kidney disease 1 | DOID:0110858 |
OMIM:173900 |
J:43193 , J:52573 , J:72627 | |
