Analysis Tools
muscle
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• formation of smooth muscle layers in gallbladders is delayed and defective with smooth muscle cells distributed randomly and irregularly with a swirling pattern distinct from wild-type mice at E17
• E13.5 gallbladder explants grown in an in vitro culture system show poor development of the smooth muscle layer
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mortality/aging
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• perinatal lethality in about 90% of pups after the N5 generation of the backcross onto C57BL/6
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• mice maintained at F8-9 backcross to C57BL/6 show approximate 70% neonatal lethality; remaining mice survive to adulthood
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liver/biliary system
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• defects in development of the bile duct systems during late-organogenic stages
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• 21 of 22 fetuses show ectopic extrahepatic ducts in the cystic duct region
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• defects in development of the gallbladder during late-organogenic stages
(J:194071)
• gallbladder hypoplasia is seen in almost all fetuses and is seen as early as E15.5
(J:194071)
• however, lung, pancreas, esophagus, stomach, duodenum and intestine appear normal
(J:194071)
• severe hypotrophy of the gallbladder
(J:241569)
• E13.5 gallbladder explants grown in an in vitro culture system show poor development with only a single-layered cuboidal epithelium without any epithelial fold formation and poor development of the smooth muscle layer
(J:241569)
• gallbladder explants incubated with SHH-soaked beads show rescue of the gallbladder developmental defects
(J:241569)
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• hypoplasia of the gallbladder epithelium as early as E15.5-16.5
(J:194071)
• gallbladder forms a hypotrophic, single-layered cuboidal epithelium with no epithelial fold formation by E17.5 and reduced height compared to a pseudostratified columnar epithelium in wild-type mice
(J:194071)
• PCNA-positive indices and Ki-67 and BrdU-labeling indices in the gallbladder epithelia are reduced at E15.5
(J:194071)
• epithelial cell deciduation in the gallbladder
(J:194071)
• frequencies of primary cilia in the gallbladder epithelia are increased
(J:194071)
• organ culture of gallbladder primordia shows defective elongation and shredding of epithelial cells in bile duct epithelia
(J:194071)
• gallbladder epithelium exhibits cystic duct-like phenotypes
(J:241569)
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• in surviving adults
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• formation of smooth muscle layers in gallbladders is delayed and defective with smooth muscle cells distributed randomly and irregularly with a swirling pattern distinct from wild-type mice at E17
• E13.5 gallbladder explants grown in an in vitro culture system show poor development of the smooth muscle layer
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• marker analysis indicates perinatal onset of hepatic inflammation in livers during E16.5-E17.5 indicating acute hepatitis in fetuses
• Background Sensitivity: hepatitis is more severe on the C57BL/6 background than on a mixed background
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• defects in development of liver during late-organogenic stages
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• 62.5% of fetuses backcrossed to C57BL/6 for 7-8 generations show peripheral degeneration of liver lobules with varying severity at E17.5
• peripheral degeneration of liver lobules is first seen at E16.5-E17 and degeneration rapidly expands toward the central proximal region of the lobules
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• endoplasmic reticulum enlargement in the cytoplasmic region facing the bile canaliculi in the hepatocytes around the degenerative region
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• liver weight is reduced at E16.5
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• development of cholestasis at E16.5-17.5
(J:194071)
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• gallbladder epithelial cells are occasionally detached from the gallbladder wall and accumulate inside the lumina of the cystic and extrahepatic duct where these cells cause stenosis and atresia in the cystic and extrahepatic ducts to varying degrees
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• KCl treatment causes no contraction of the fetal gallbladder at E17.5 in mildly and severely affected mutants, while in the severely affected mice, KCl-induced contraction is reduced
• -autonomous gallbladder contraction is reduced at E17.5
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• marker analysis indicates onset of cholecytitis in gallbladder during fetal stages
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endocrine/exocrine glands
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• defects in development of the bile duct systems during late-organogenic stages
|
|
• 21 of 22 fetuses show ectopic extrahepatic ducts in the cystic duct region
|
|
• defects in development of the gallbladder during late-organogenic stages
(J:194071)
• gallbladder hypoplasia is seen in almost all fetuses and is seen as early as E15.5
(J:194071)
• however, lung, pancreas, esophagus, stomach, duodenum and intestine appear normal
(J:194071)
• severe hypotrophy of the gallbladder
(J:241569)
• E13.5 gallbladder explants grown in an in vitro culture system show poor development with only a single-layered cuboidal epithelium without any epithelial fold formation and poor development of the smooth muscle layer
(J:241569)
• gallbladder explants incubated with SHH-soaked beads show rescue of the gallbladder developmental defects
(J:241569)
|
|
• hypoplasia of the gallbladder epithelium as early as E15.5-16.5
(J:194071)
• gallbladder forms a hypotrophic, single-layered cuboidal epithelium with no epithelial fold formation by E17.5 and reduced height compared to a pseudostratified columnar epithelium in wild-type mice
(J:194071)
• PCNA-positive indices and Ki-67 and BrdU-labeling indices in the gallbladder epithelia are reduced at E15.5
(J:194071)
• epithelial cell deciduation in the gallbladder
(J:194071)
• frequencies of primary cilia in the gallbladder epithelia are increased
(J:194071)
• organ culture of gallbladder primordia shows defective elongation and shredding of epithelial cells in bile duct epithelia
(J:194071)
• gallbladder epithelium exhibits cystic duct-like phenotypes
(J:241569)
|
|
• in surviving adults
|
|
• formation of smooth muscle layers in gallbladders is delayed and defective with smooth muscle cells distributed randomly and irregularly with a swirling pattern distinct from wild-type mice at E17
• E13.5 gallbladder explants grown in an in vitro culture system show poor development of the smooth muscle layer
|
homeostasis/metabolism
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• levels of serum ALT are elevated at E17
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• serum levels of ALP are elevated at E17
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• intrahepatic levels of bile acids is elevated in livers at E17
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immune system
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• marker analysis indicates onset of cholecytitis in gallbladder during fetal stages
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• marker analysis indicates perinatal onset of hepatic inflammation in livers during E16.5-E17.5 indicating acute hepatitis in fetuses
• Background Sensitivity: hepatitis is more severe on the C57BL/6 background than on a mixed background
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| biliary atresia | DOID:13608 |
OMIM:210500 |
J:194071 , J:241569 | |
