Mouse Genome Informatics
hm1
    Jag1tm1Grid/Jag1tm1Grid
involves: 129S1/Sv * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• death occurs at approximately E10.5 due to widespread hemorrhages
• normal appearance at E9.5, and widespread necrosis is observed at E11.5
• no defects in somitogenesis are observed

embryogenesis
• large blood vessels are absent from the yolk sacs
• a pale yolk sac is seen at E10.5

cardiovascular system
• the vascular network in the forebrain of mutant embryos is not as well developed as in controls
• large blood vessels of the head have an abnormal appearance and a reduced diameter
• the primary vascular plexus of the yolk sac does not remodel into large blood vessels
• large blood vessels are absent from the yolk sacs
• widespread, including embryonic and extraembryonic tissues observed at E10.5


Mouse Genome Informatics
ht2
    Jag1tm1Grid/Jag1+
involves: 129S1/Sv * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• Background Sensitivity: eye phenotypes are described as fully penetrant on an 80% C57BL/6 genetic background and incompletely penetrant on a mixed background
• iris coloboma

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Alagille Syndrome 1; ALGS1 118450 J:54907


Mouse Genome Informatics
cn3
    Jag1tm1Grid/Jag1tm2Grid
Foxg1tm1(cre)Skm/Foxg1+

involves: 129P2/OlaHsd * 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants survive through E18.5

hearing/vestibular/ear
N
• at E15.5, inner ear structures not associated with sensory formation such as endolymphatic duct and sac, and crus are not affected (J:115783)
• formation of prosensory domain is disrupted by E18.5
• severe hair cell patterning defects are observed at E18.5
• no clear formation of rows or distinction between inner and outer hair cells is observed in midbasal regions of the organ of Corti; hair cells form in patches
• at E16.5, patterns look similar to those at E18.5 with patches of hair cells in midbasal regions and absent hair cells in very basal regions
• in middle portion of cochlea, patterning of inner and sparse outer hair cells is abnormal
• in apical turn of cochlea, there are only two rows instead of four rows of hair cells
• no hair cell formation is observed in basal turns of cochlea; at E18.5, hair cells and supporting cells are absent in very basal region of cochlea
• no outer hair cells or supporting Deiter's cells are present in apex of cochlea
• at E18.5, tunnel of Corti is not apparent
• semicircular canals are mostly absent, with only a small portion of lateral semicircular canal present at E15.5
• cristae and ampullae are missing or severely disrupted by E14.5 in homozygotes
• at E15.5, only a small portion of the anterior canal is present in homozygotes
• at E15.5, semicircular canals are largely absent
• structure is extremely small, with few differentiating hair cells; severe disruption of differentiation of utricular macula is observed
• observed at E13.5
• at E13.5, saccule appears misshapen
• at E18.5, saccule and macula are relatively normal, but entire saccular structure is shaped differently compared to controls

nervous system
• severe hair cell patterning defects are observed at E18.5
• no clear formation of rows or distinction between inner and outer hair cells is observed in midbasal regions of the organ of Corti; hair cells form in patches
• at E16.5, patterns look similar to those at E18.5 with patches of hair cells in midbasal regions and absent hair cells in very basal regions
• in middle portion of cochlea, patterning of inner and sparse outer hair cells is abnormal
• in apical turn of cochlea, there are only two rows instead of four rows of hair cells
• no hair cell formation is observed in basal turns of cochlea; at E18.5, hair cells and supporting cells are absent in very basal region of cochlea
• no outer hair cells or supporting Deiter's cells are present in apex of cochlea


Mouse Genome Informatics
cn4
    Jag1tm1Grid/Jag1tm1.1Loo
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
liver/biliary system
• at 8 weeks of age, some mice have dilated bile tracts and expanded portal tracts
• cytokeratin staining also shows irregular, dilated ducts surrounding the periphery of many portal tracts
• bile stasis is identified within the lumina of several proliferating ducts
• diffuse bile duct proliferation is observed around small and large bile ducts by 4 weeks of age
• by 12 weeks of age, 50% of mice have bile duct proliferation with these ducts appearring small and slit-like

endocrine/exocrine glands
• at 8 weeks of age, some mice have dilated bile tracts and expanded portal tracts
• cytokeratin staining also shows irregular, dilated ducts surrounding the periphery of many portal tracts


Mouse Genome Informatics
cn5
    Jag1tm1Jlew/Jag1tm1Grid
Tg(Pdgfb-icre/ERT2)1Frut/0

involves: 129S1/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• with postnatal tamoxifen treatment from P1-P3, pups are generally smaller than tamoxifen-treated control littermates

vision/eye
• perpendicular sprouting and neovascularization of the deeper retina are strongly compromised with tamoxifen treatment between P5 and P9

cardiovascular system
N
• stability of blood vessels is not affected in mutants with tamoxifen treatment at P1; stability of established vessels in the superficial capillary plexus is not affected with tamoxifen administration between P5 and P9 (J:157345)
• postnatal tamoxifen treatment from P1-P3 results in decreased coverage of retinal arteries by vascular smooth muscle cells; however pericyte coverage of capillary beds shows no change
• perpendicular sprouting and neovascularization of the deeper retina are strongly compromised with tamoxifen treatment between P5 and P9
• postnatal tamoxifen treatment from P1-P3 to delete Jag1 in endothelial cells results in significant decreases in numbers of filopodia and filopodia-extending endothelial tip cells
• postnatal tamoxifen treatment from P1-P3 results in strong inhibition of angiogenesis in the retina resulting in reduced branching and delayed extension toward the periphery


Mouse Genome Informatics
cn6
    Jag1tm1Grid/Jag1tm2Grid
Tg(Tagln-cre)1Her/0

involves: 129S1/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 50% of mutants die by P1
• no mutants survive past P2

cardiovascular system
• 95% of mutants exhibit patent ductus arteriosus
• defects in vascular smooth muscle cell differentiation in the outer layers of the medial wall of the ductus arteriosus and descending aorta at E17.5 when the ductus arteriosus is still patent, however the ascending limb of the aorta and the pulmonary artery trunk have normal vascular smooth muscle cell differentiation

homeostasis/metabolism

muscle
• defects in vascular smooth muscle cell differentiation in the outer layers of the medial wall of the ductus arteriosus and descending aorta at E17.5 when the ductus arteriosus is still patent, however the ascending limb of the aorta and the pulmonary artery trunk have normal vascular smooth muscle cell differentiation

Mouse Models of Human Disease
OMIM IDRef(s)
Patent Ductus Arteriosus 607411 J:166769


Mouse Genome Informatics
cx7
    Jag1tm1Grid/Jag1+
Notch2tm3.1Grid/Notch2+

B6.129S1-Jag1tm1Grid Notch2tm3.1Grid
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
liver/biliary system
• severe decrease in the number of biliary cells in the periportal regions at P0
• bile duct paucity at P0

endocrine/exocrine glands
• bile duct paucity at P0


Mouse Genome Informatics
cx8
    Jag1tm1Grid/Jag1+
Poglut1Gt(IST10323G11)Tigm/Poglut1+

B6.Cg-Jag1tm1Grid Poglut1Gt(IST10323G11)Tigm
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
liver/biliary system
• severe decrease in the number of biliary cells in the periportal regions at P0
• bile duct paucity at P0

endocrine/exocrine glands
• bile duct paucity at P0


Mouse Genome Informatics
cx9
    Jag1tm1Grid/Cm
involves: 101/H * 129S1/Sv * C3H/He * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system

nervous system


Mouse Genome Informatics
cx10
    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
cx11
    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