Phenotypes Associated with This Genotype

Genotype
MGI:2384061

• Allelic Composition: Jag1^tm1Grid/Jag1⁺; Notch2^tm1Grid/Notch2⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

postnatal lethality, incomplete penetrance ( J:74574 )

• approximately 50% of the double heterozygotes died within the first week after birth

renal/urinary system

abnormal glomerular capillary morphology ( J:67157 )

• about a quarter of the glomeruli present lacked glomerular capillary tufts and exhibited capillary aneuryisms similar to those observed in Notch2^tm1Grid/Notch2^tm1Grid homozygous mutant kidneys

kidney microaneurysm ( J:74574 )

• about a quarter of the glomeruli present exhibited capillary aneuryisms

decreased renal glomerulus number ( J:74574 )

• greatly reduced

small kidney ( J:67157 )

• kidneys of the double heterozygotes were about half the size of kidneys from the controls

liver/biliary system

abnormal bile duct development ( J:74574 )

• 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 liver morphology ( J:74574 )

• abnormal proliferation of cells adjacent to the portal veins and bile pigment accumulation in the hepatic parenchyma

cholestasis ( J:74574 )

• chronic; indicated by elevated levels of alanine aminotransferase and alkaline phosphatase

jaundice ( J:74574 )

homeostasis/metabolism

increased blood urea nitrogen level ( J:74574 )

• elevated blood urea nitrogen levels

increased circulating alanine transaminase level ( J:74574 )

• elevated levels of alanine aminotransferase, indicative of liver and biliary dysfunction

increased circulating alkaline phosphatase level ( J:74574 )

• elevated levels of alkaline phosphatase, indicative of liver and biliary dysfunction

cardiovascular system

pulmonary artery stenosis ( J:74574 )

• narrowing of the pulmonary artery; incomplete penetrance; observed in 6 of 9 animals

abnormal glomerular capillary morphology ( J:67157 )

• about a quarter of the glomeruli present lacked glomerular capillary tufts and exhibited capillary aneuryisms similar to those observed in Notch2^tm1Grid/Notch2^tm1Grid homozygous mutant kidneys

kidney microaneurysm ( J:74574 )

• about a quarter of the glomeruli present exhibited capillary aneuryisms

overriding aortic valve ( J:74574 )

• dextropositioning (overriding) of the aorta

atrial septal defect ( J:74574 )

• incomplete penetrance; observed in 12 of 14 animals

ventricular septal defect ( J:74574 )

• incomplete penetrance; observed in 6 of 14 animals

ventricular hypoplasia ( J:74574 )

• right ventricular hypoplasia

growth/size/body

postnatal growth retardation ( J:74574 )

vision/eye

abnormal anterior eye segment morphology ( J:74574 )

• eye defects similar to those in Jag1^tm1Grid homozygous mice

endocrine/exocrine glands

abnormal bile duct development ( J:74574 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Alagille syndrome		DOID:9245	OMIM:118450 OMIM:610205	J:74574