Mouse Genome Informatics
hm1
    Notch2tm1Grid/Notch2tm1Grid
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
• incomplete penetrance; many animals die within the first 24 hours after birth
• incomplete penetrance; many embryos die between E12.5-E15.5 and become necrotic
• at stages after E16.5, only 12% of the embryos are homozygous mutants

renal/urinary system
• the glomerular capillary tuft sometimes appears as a capillary aneurysm-like structure that releases red blood cells into the Bowman's capsule
• at E15.5, an increased number of apoptotic cells was observed in the kidney
• at E15.5, no proliferating cells were observed inside the abnormal glomeruli whereas these cells were detected in control mice
• vascular lesions evident at the cortical surface
• cells that expressed markers of podocyte differentiation were clumped together in the center of the glomerulus, and did not form the cup-shaped epithelial layer observed in the controls
• at E16.5, no morphologically normal glomeruli present
• frequently, the glomerulus appears as a disorganized clump of cells
• the glomerular capillary tuft sometimes appears as a capillary aneurysm-like structure that releases red blood cells into the Bowman's capsule
• few endothelial cells were present in the abnormal mutant glomeruli
• absence of cells that express markers of mesangial cell differentiation in the abnormal glomeruli
• at E16.5, kidneys were smaller than controls

cardiovascular system
• few endothelial cells were present in the abnormal mutant glomeruli
• the glomerular capillary tuft sometimes appears as a capillary aneurysm-like structure that releases red blood cells into the Bowman's capsule
• reduced myocardial trabeculation evident by E12.5 and thereafter
• in embryos surviving past E11.5, myocardial hypoplasia is evident, with hemorrhaging and edema
• 40% of embryos exhibited pericardial effusion at E11.5
• 40% of embryos exhibited widespread hemorrhaging at E11.5; also evident in later embryonic stages

vision/eye
• pronounced asymmetry of the eyes
• aberrant bulbous structure at the terminus of the hyaloid artery, with many small capillaries emanating from it
• retrolenticular hyperplasia
• bilateral

homeostasis/metabolism
• 40% of embryos exhibited pericardial effusion at E11.5
• 50% of embryos at E13.5 showed edema and hemorrhaging vessels near skin surface

growth/size
• by E11.5, 40% of embryos showed growth retardation

liver/biliary system
• bile duct epithelial cell differentiation defects occur

muscle
• reduced myocardial trabeculation evident by E12.5 and thereafter

embryogenesis
• by E11.5, 40% of embryos showed growth retardation

endocrine/exocrine glands
• bile duct epithelial cell differentiation defects occur

integument
• 50% of embryos at E13.5 showed edema and hemorrhaging vessels near skin surface

cellular
• at E15.5, an increased number of apoptotic cells was observed in the kidney
• at E15.5, no proliferating cells were observed inside the abnormal glomeruli whereas these cells were detected in control mice


Mouse Genome Informatics
cn2
    Jag1tm1.1Loo/Jag1+
Notch2tm1Grid/Notch2+
Tg(Alb1-cre)1Khk/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• no abnormal phenotype was observed including in the bile ducts


Mouse Genome Informatics
cx3
    Jag1tm1Grid/Jag1+
Notch2tm1Grid/Notch2+

involves: 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
liver/biliary system
• at P7, very little bile duct is present
• postnatal bile duct morphogenesis is defective although differentiation of bile duct precursors is normal

endocrine/exocrine glands
• at P7, very little bile duct is present
• postnatal bile duct morphogenesis is defective although differentiation of bile duct precursors is normal


Mouse Genome Informatics
cx4
    Notch2tm1Grid/Notch2+
Dll1tm1Gos/Dll1+

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
N
• no kidney defects were observed despite expression of both genes in the developing glomerulus (J:67157)


Mouse Genome Informatics
cx5
    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


Mouse Genome Informatics
cx6
    Notch1tm1Grid/Notch1tm1Grid
Notch2tm1Grid/Notch2tm1Grid

involves: 129S1/Sv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• reversed and ventral loops

embryogenesis
• reversed axial rotation