Mouse Genome Informatics
cx
    Jag1tm1Grid/Jag1+
Notch2tm1Grid/Notch2+

involves: 129S1/Sv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• approximately 50% of the double heterozygotes died within the first week after birth

renal/urinary system
• about a quarter of the glomeruli present lacked glomerular capillary tufts and exhibited capillary aneuryisms similar to those observed in Notch2tm1Grid/Notch2tm1Grid homozygous mutant kidneys
• about a quarter of the glomeruli present exhibited capillary aneuryisms
• kidneys of the double heterozygotes were about half the size of kidneys from the controls

liver/biliary system
• defects in intrahepatic bile duct differentiation
• few morphologically identifiable bile ducts were present
• expression of markers for bile duct epithelial cells was detected; small numbers of these cells were adjacent to the portal veins, but these cells were not arranged into patent epithelial ducts
• expression of markers for hepatoblast cells that are precursors for bile duct epithelial cells indicates that no differences in the number or distribution of these precursors is apparent
• abnormal proliferation of cells adjacent to the portal veins and bile pigment accumulation in the hepatic parenchyma
• chronic; indicated by elevated levels of alanine aminotransferase and alkaline phosphatase

homeostasis/metabolism
• elevated blood urea nitrogen levels
• elevated levels of alanine aminotransferase, indicative of liver and biliary dysfunction
• elevated levels of alkaline phosphatase, indicative of liver and biliary dysfunction

cardiovascular system
• narrowing of the pulmonary artery; incomplete penetrance; observed in 6 of 9 animals
• about a quarter of the glomeruli present lacked glomerular capillary tufts and exhibited capillary aneuryisms similar to those observed in Notch2tm1Grid/Notch2tm1Grid homozygous mutant kidneys
• about a quarter of the glomeruli present exhibited capillary aneuryisms
• dextropositioning (overriding) of the aorta
• incomplete penetrance; observed in 12 of 14 animals
• incomplete penetrance; observed in 6 of 14 animals
• right ventricular hypoplasia

growth/size

vision/eye
• eye defects similar to those in Jag1tm1Grid homozygous mice

endocrine/exocrine glands
• defects in intrahepatic bile duct differentiation
• few morphologically identifiable bile ducts were present
• expression of markers for bile duct epithelial cells was detected; small numbers of these cells were adjacent to the portal veins, but these cells were not arranged into patent epithelial ducts
• expression of markers for hepatoblast cells that are precursors for bile duct epithelial cells indicates that no differences in the number or distribution of these precursors is apparent

Mouse Models of Human Disease
OMIM IDRef(s)
Alagille Syndrome 1; ALGS1 118450 J:74574