Phenotypes associated with this allele

• Allele Symbol: Jag1^tm1Grid
• Allele Name: targeted mutation 1, Tom Gridley
• Allele ID: MGI:1857713
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Jag1^tm1Grid/Jag1^tm1Grid	involves: 129S1/Sv * C57BL/6 * FVB	MGI:2384052
ht2	Jag1^tm1Grid/Jag1^+	involves: 129S1/Sv * C57BL/6 * FVB	MGI:2384058
cn3	Jag1^tm1Grid/Jag1^tm2Grid Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:3693201
cn4	Jag1^tm1Grid/Jag1^tm1.1Loo Tg(Alb1-cre)1Khk/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3848171
cn5	Jag1^tm1Jlew/Jag1^tm1Grid Tg(Pdgfb-icre/ERT2,-EGFP)1Frut/0	involves: 129S1/Sv * C57BL/6 * CBA	MGI:4437857
cn6	Jag1^tm1Grid/Jag1^tm2Grid Tg(Tagln-cre)1Her/0	involves: 129S1/Sv * C57BL/6 * SJL	MGI:4867007
cx7	Jag1^tm1Grid/Jag1^+ Notch2^tm3.1Grid/Notch2^+	B6.129S1-Jag1^tm1Grid Notch2^tm3.1Grid	MGI:5004909
cx8	Jag1^tm1Grid/Jag1^+ Poglut1^Gt(IST10323G11)Tigm/Poglut1^+	B6.Cg-Jag1^tm1Grid Poglut1^Gt(IST10323G11)Tigm	MGI:5004906
cx9	Jag1^tm1Grid/Cm	involves: 101/H * 129S1/Sv * C3H/He * C57BL/6 * FVB/N	MGI:3588033
cx10	Jag1^tm1Grid/Jag1^+ Notch2^tm1Grid/Notch2^+	involves: 129S1/Sv	MGI:3778810
cx11	Jag1^tm1Grid/Jag1^+ Notch2^tm1Grid/Notch2^+	involves: 129S1/Sv * C57BL/6J	MGI:2384061

Genotype
MGI:2384052

hm1

• Allelic Composition: Jag1^tm1Grid/Jag1^tm1Grid
• Genetic Background: involves: 129S1/Sv * C57BL/6 * FVB

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:54907 )

• 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

embryo

pale yolk sac ( J:54907 )

• a pale yolk sac is seen at E10.5

abnormal vitelline vascular remodeling ( J:54907 )

• large blood vessels are absent from the yolk sacs

cardiovascular system

abnormal vascular development ( J:54907 )

• 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

hemorrhage ( J:54907 )

• widespread, including embryonic and extraembryonic tissues observed at E10.5

Genotype
MGI:2384058

ht2

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

vision/eye

abnormal eye morphology ( J:54907 )

• Background Sensitivity: eye phenotypes are described as fully penetrant on an 80% C57BL/6 genetic background and incompletely penetrant on a mixed background

abnormal placement of pupils ( J:54907 )

irregularly shaped pupil ( J:54907 )

iris coloboma ( J:54907 )

• iris coloboma

cornea opacity ( J:54907 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Alagille syndrome	DOID:9245	OMIM:118450 OMIM:610205	J:54907

Genotype
MGI:3693201

cn3

• Allelic Composition: Jag1^tm1Grid/Jag1^tm2Grid; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

mortality/aging

perinatal lethality, complete penetrance ( J:115783 )

• mutants survive through E18.5

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:115783 )

N • at E15.5, inner ear structures not associated with sensory formation such as endolymphatic duct and sac, and crus are not affected

abnormal cochlea morphology ( J:115783 )

• formation of prosensory domain is disrupted by E18.5

abnormal cochlear hair cell morphology ( J:115783 )

• 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

abnormal cochlear hair cell number ( J:115783 )

• in apical turn of cochlea, there are only two rows instead of four rows of hair cells

absent cochlear hair cells ( J:115783 )

• 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

abnormal cochlear outer hair cell morphology ( J:115783 )

• no outer hair cells or supporting Deiter's cells are present in apex of cochlea

absent tunnel of Corti ( J:115783 )

• at E18.5, tunnel of Corti is not apparent

decreased cochlea coiling ( J:115783 )

abnormal lateral semicircular canal morphology ( J:115783 )

• semicircular canals are mostly absent, with only a small portion of lateral semicircular canal present at E15.5

abnormal crista ampullaris morphology ( J:115783 )

• cristae and ampullae are missing or severely disrupted by E14.5 in homozygotes

abnormal superior semicircular canal morphology ( J:115783 )

• at E15.5, only a small portion of the anterior canal is present in homozygotes

absent semicircular canals ( J:115783 )

• at E15.5, semicircular canals are largely absent

abnormal utricular macula morphology ( J:115783 )

• structure is extremely small, with few differentiating hair cells; severe disruption of differentiation of utricular macula is observed

small utricle ( J:115783 )

• observed at E13.5

abnormal vestibular saccule morphology ( J:115783 )

• 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

abnormal cochlear hair cell morphology ( J:115783 )

• 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

abnormal cochlear hair cell number ( J:115783 )

• in apical turn of cochlea, there are only two rows instead of four rows of hair cells

absent cochlear hair cells ( J:115783 )

• 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

abnormal cochlear outer hair cell morphology ( J:115783 )

• no outer hair cells or supporting Deiter's cells are present in apex of cochlea

Genotype
MGI:3848171

cn4

• Allelic Composition: Jag1^tm1Grid/Jag1^tm1.1Loo; Tg(Alb1-cre)1Khk/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

liver/biliary system

bile duct proliferation ( J:149131 )

• 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

dilated bile duct ( J:149131 )

• 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

abnormal bile secretion ( J:149131 )

• bile stasis is identified within the lumina of several proliferating ducts

endocrine/exocrine glands

bile duct proliferation ( J:149131 )

• 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

dilated bile duct ( J:149131 )

• 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

Genotype
MGI:4437857

cn5

• Allelic Composition: Jag1^tm1Jlew/Jag1^tm1Grid; Tg(Pdgfb-icre/ERT2,-EGFP)1Frut/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

growth/size/body

postnatal growth retardation ( J:157345 )

• with postnatal tamoxifen treatment from P1-P3, pups are generally smaller than tamoxifen-treated control littermates

vision/eye

abnormal retina vasculature morphology ( J:157345 )

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

cardiovascular system

cardiovascular system phenotype ( J:157345 )

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

abnormal blood vessel morphology ( 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

abnormal retina vasculature morphology ( J:157345 )

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

abnormal angiogenesis ( J:157345 )

• 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

decreased angiogenesis ( J:157345 )

• 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

Genotype
MGI:4867007

cn6

• Allelic Composition: Jag1^tm1Grid/Jag1^tm2Grid; Tg(Tagln-cre)1Her/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:166769 )

• no mutants survive past P2

perinatal lethality, incomplete penetrance ( J:166769 )

• 50% of mutants die by P1

cardiovascular system

retroesophageal right subclavian artery ( J:166769 )

• seen in some mutants

patent ductus arteriosus ( J:166769 )

• 95% of mutants exhibit patent ductus arteriosus

abnormal vascular smooth muscle morphology ( J:166769 )

• 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

cyanosis ( J:166769 )

muscle

abnormal vascular smooth muscle morphology ( J:166769 )

• 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

cellular

patent ductus arteriosus ( J:166769 )

• 95% of mutants exhibit patent ductus arteriosus

Genotype
MGI:5004909

cx7

• Allelic Composition: Jag1^tm1Grid/Jag1⁺; Notch2^tm3.1Grid/Notch2⁺
• Genetic Background: B6.129S1-Jag1^tm1Grid Notch2^tm3.1Grid

liver/biliary system

abnormal biliary tract morphology ( J:171432 )

• severe decrease in the number of biliary cells in the periportal regions at P0

abnormal bile duct morphology ( J:171432 )

• bile duct paucity at P0

endocrine/exocrine glands

abnormal bile duct morphology ( J:171432 )

• bile duct paucity at P0

Genotype
MGI:5004906

cx8

• Allelic Composition: Jag1^tm1Grid/Jag1⁺; Poglut1^{Gt(IST10323G11)Tigm}/Poglut1⁺
• Genetic Background: B6.Cg-Jag1^tm1Grid Poglut1^{Gt(IST10323G11)Tigm}

liver/biliary system

abnormal biliary tract morphology ( J:171432 )

• severe decrease in the number of biliary cells in the periportal regions at P0

abnormal bile duct morphology ( J:171432 )

• bile duct paucity at P0

endocrine/exocrine glands

abnormal bile duct morphology ( J:171432 )

• bile duct paucity at P0

Genotype
MGI:3588033

cx9

• Allelic Composition: Jag1^tm1Grid/Cm
• Genetic Background: involves: 101/H * 129S1/Sv * C3H/He * C57BL/6 * FVB/N

cardiovascular system

intracranial hemorrhage ( J:54907 )

nervous system

intracranial hemorrhage ( J:54907 )

Genotype
MGI:3778810

cx10

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

liver/biliary system

abnormal bile duct morphology ( J:133171 )

• at P7, very little bile duct is present

abnormal bile duct development ( J:133171 )

• postnatal bile duct morphogenesis is defective although differentiation of bile duct precursors is normal

endocrine/exocrine glands

abnormal bile duct morphology ( J:133171 )

• at P7, very little bile duct is present

abnormal bile duct development ( J:133171 )

• postnatal bile duct morphogenesis is defective although differentiation of bile duct precursors is normal

Genotype
MGI:2384061

cx11

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

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