Phenotypes associated with this allele

• Allele Symbol: Notch1^tm1Grid
• Allele Name: targeted mutation 1, Tom Gridley
• Allele ID: MGI:1857877
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Notch1^tm1Grid/Notch1^tm1Grid	involves: 129S1/Sv * C57BL/6	MGI:2175158
ht2	Notch1^tm1Grid/Notch1^+	involves: 129S1/Sv * C57BL/6	MGI:3695940
cn3	Notch1^tm1Grid/Notch1^tm2Rko Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129 * C57BL/6J * Swiss Webster	MGI:3776429
cn4	Notch1^tm1Con/Notch1^tm1Grid Tg(Pax2-cre)1Akg/0	involves: 129S1/Sv * 129X1/SvJ	MGI:3713803
cx5	Notch1^tm1Grid/Notch1^+ Notch3^tm1Grid/Notch3^tm1Grid	involves: 129S1/Sv * C57BL/6	MGI:5771892
cx6	Notch1^tm1Grid/Notch1^tm1Grid Notch4^tm1Grid/Notch4^tm1Grid	involves: 129S1/Sv * C57BL/6	MGI:3580253
cx7	Notch1^tm1Grid/Notch1^+ Notch4^tm1Grid/Notch4^tm1Grid	involves: 129S1/Sv * C57BL/6	MGI:3580252
cx8	Notch1^tm1Grid/Notch1^tm1Grid Notch2^tm1Grid/Notch2^tm1Grid	involves: 129S1/Sv * C57BL/6J	MGI:3580251
cx9	Tle5^tm1Grid/Tle5^tm1Grid Notch1^tm1Grid/Notch1^+	involves: 129S1/Sv * C57BL/6J	MGI:3039488
cx10	Notch1^tm1Grid/Notch1^tm1Grid Notch3^tm1Grid/Notch3^tm1Grid	Not Specified	MGI:2687026

Genotype
MGI:2175158

hm1

• Allelic Composition: Notch1^tm1Grid/Notch1^tm1Grid
• Genetic Background: involves: 129S1/Sv * C57BL/6

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:17509 )

• many resorbed embryos by E10.5, surviving embryos are severely retarded but with beating hearts in distended pericardial sacs

• all homozygous embryos are resorbed at E11.5

cardiovascular system

abnormal dorsal aorta morphology ( J:62571 )

• collapsed appearance of dorsal aortae

abnormal placenta vasculature ( J:62571 )

• embryonic blood vessels fail to invade trophoblast

decreased angiogenesis ( J:62571 )

• vasculogenesis was normal but subsequent remodeling failed

absent vitelline blood vessels ( J:62571 )

• pale yolk sacs lacking obvious blood vessels

embryo

abnormal placenta vasculature ( J:62571 )

• embryonic blood vessels fail to invade trophoblast

absent vitelline blood vessels ( J:62571 )

• pale yolk sacs lacking obvious blood vessels

embryonic growth retardation ( J:17509 )

• normal at E8.5 but retarded at E9.5 (14-16 somites rather than 20-25)

pale yolk sac ( J:62571 )

• pale yolk sacs lacking obvious blood vessels

growth/size/body

embryonic growth retardation ( J:17509 )

• normal at E8.5 but retarded at E9.5 (14-16 somites rather than 20-25)

Genotype
MGI:3695940

ht2

• Allelic Composition: Notch1^tm1Grid/Notch1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

cardiovascular system

abnormal retina blood vessel morphology ( J:227333 )

• increase in vessel density in retinas at P5

• retinal capillaries exhibit gaps in pericyte coverage

hearing/vestibular/ear

increased cochlear outer hair cell number ( J:62727 )

• at P1, neonatal heterozygotes display numerous regions of the cochlear sensory epithelium with 4 rather than 3 rows of OHCs

• significant increases are noted in both the numbers of regions of fourth row OHCs, as well as the total number of fourth row OHCs

• however, patterning of OHC rows is normal, and no supernumerary hair cells are observed in the IHC row

vision/eye

abnormal retina blood vessel morphology ( J:227333 )

• increase in vessel density in retinas at P5

• retinal capillaries exhibit gaps in pericyte coverage

nervous system

increased cochlear outer hair cell number ( J:62727 )

• at P1, neonatal heterozygotes display numerous regions of the cochlear sensory epithelium with 4 rather than 3 rows of OHCs

• significant increases are noted in both the numbers of regions of fourth row OHCs, as well as the total number of fourth row OHCs

• however, patterning of OHC rows is normal, and no supernumerary hair cells are observed in the IHC row

Genotype
MGI:3776429

cn3

• Allelic Composition: Notch1^tm1Grid/Notch1^tm2Rko; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129 * C57BL/6J * Swiss Webster

hearing/vestibular/ear

increased cochlear inner hair cell number ( J:132241 )

• increases in inner hair cell number are more than in Dll1^tm1Gos/Dll1^tm2Gos Jag2^tm1Grid/Jag2^tm1Grid mice

decreased organ of Corti supporting cell number ( J:132241 )

• decreases in inner hair cell number are slightly than in Dll1^tm1Gos/Dll1^tm2Gos Jag2^tm1Grid/Jag2^tm1Grid mice or Dll1^tm1Gos Jag2^tm1Grid homozygotes

nervous system

increased cochlear inner hair cell number ( J:132241 )

• increases in inner hair cell number are more than in Dll1^tm1Gos/Dll1^tm2Gos Jag2^tm1Grid/Jag2^tm1Grid mice

Genotype
MGI:3713803

cn4

• Allelic Composition: Notch1^tm1Con/Notch1^tm1Grid; Tg(Pax2-cre)1Akg/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:119907 )

• embryos are normal at E12.5, but die at E13.5

renal/urinary system

renal/urinary system phenotype ( J:119907 )

N • metanephroi appear normal morphologically and histologically when cultured at E12.5

cardiovascular system

abnormal vascular development ( J:119907 )

internal hemorrhage ( J:119907 )

Genotype
MGI:5771892

cx5

• Allelic Composition: Notch1^tm1Grid/Notch1⁺; Notch3^tm1Grid/Notch3^tm1Grid
• Genetic Background: involves: 129S1/Sv * C57BL/6

vision/eye

abnormal retina vasculature morphology ( J:227333 )

• increase in the number of endothelial tip cells at the angiogenic front of P5 retinas

• P8 retinas display areas of sheet-like endothelium that lacks defined arterioles and venules

• retinas show extensive presence of arteriovenous shunts and vascular tangles

abnormal retina blood vessel morphology ( J:227333 )

• increase in vessel density in retinas compared to either single mutant

• reduction in vessel outgrowth at P5 in retinas

• retinal capillaries exhibit gaps in pericyte coverage

• P5 retinas show altered vessel structures with pericytes located at a greater distance from the vessel lumen, indicative of pericyte dissociation

• the intracellular region between pericytes and endothelial cells appears wider, less dense and has visible large open spaces indicating that pericytes fail to associate properly with the endothelium

• retinal vessels of P5 mice show loss of mural cells

• P5 retinal capillaries exhibit numerous granular osmiophilic material in the vicinity of pericytes and not associated with endothelial cells

cardiovascular system

abnormal retina vasculature morphology ( J:227333 )

• increase in the number of endothelial tip cells at the angiogenic front of P5 retinas

• P8 retinas display areas of sheet-like endothelium that lacks defined arterioles and venules

• retinas show extensive presence of arteriovenous shunts and vascular tangles

abnormal retina blood vessel morphology ( J:227333 )

• increase in vessel density in retinas compared to either single mutant

• reduction in vessel outgrowth at P5 in retinas

• retinal capillaries exhibit gaps in pericyte coverage

• P5 retinas show altered vessel structures with pericytes located at a greater distance from the vessel lumen, indicative of pericyte dissociation

• the intracellular region between pericytes and endothelial cells appears wider, less dense and has visible large open spaces indicating that pericytes fail to associate properly with the endothelium

• retinal vessels of P5 mice show loss of mural cells

• P5 retinal capillaries exhibit numerous granular osmiophilic material in the vicinity of pericytes and not associated with endothelial cells

abnormal pericyte morphology ( J:227333 )

• a subset of pericytes in capillaries show altered cell morphology with overlapping cell processes that fail to tightly and continuously line the endothelium

• reduction in pericyte coverage and abnormal pericyte morphology along enlarged retinal venules at P5

abnormal vascular plexus formation ( J:227333 )

• at P8, mice maintain a hyper-vascularized retinal primary plexus

abnormal vascular smooth muscle morphology ( J:227333 )

• mice exhibit impaired arteriolar vascular smooth muscle cell differentiation at P5

abnormal venule morphology ( J:227333 )

• enlargement of venules in P5 retinas

arteriovenous malformation ( J:227333 )

• mice display severe retinal arteriovenous malformations

cellular

impaired basement membrane formation ( J:227333 )

• collagen IV deposition in retinal capillaries is severely disorganized and often in the open spaces of the capillary plexus and laminin deposition is abnormal indicating abnormal vascular basement membrane formation

muscle

abnormal vascular smooth muscle morphology ( J:227333 )

• mice exhibit impaired arteriolar vascular smooth muscle cell differentiation at P5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CADASIL 1		DOID:0111035	OMIM:125310	J:227333

Genotype
MGI:3580253

cx6

• Allelic Composition: Notch1^tm1Grid/Notch1^tm1Grid; Notch4^tm1Grid/Notch4^tm1Grid
• Genetic Background: involves: 129S1/Sv * C57BL/6

embryo

abnormal placenta vasculature ( J:62571 )

• embryonic blood vessels fail to invade trophoblast

absent vitelline blood vessels ( J:62571 )

• pale yolk sacs lacking obvious blood vessels

incomplete embryo turning ( J:62571 )

• did not complete embryonic turning

open neural tube ( J:62571 )

incomplete somite formation ( J:62571 )

• fewer somites formed

pale yolk sac ( J:62571 )

• pale yolk sacs lacking obvious blood vessels

cardiovascular system

abnormal dorsal aorta morphology ( J:62571 )

• dorsal aortae lack lumens

abnormal intersomitic vessel morphology ( J:62571 )

• severely disorganized intersomitic vessels

abnormal placenta vasculature ( J:62571 )

• embryonic blood vessels fail to invade trophoblast

decreased angiogenesis ( J:62571 )

• vasculogenesis was normal but subsequent remodeling failed

absent vitelline blood vessels ( J:62571 )

• pale yolk sacs lacking obvious blood vessels

abnormal vein morphology ( J:62571 )

• lacking lumens

abnormal anterior cardinal vein morphology ( J:62571 )

• anterior cardinal veins discontinuous or missing

pericardial edema ( J:62571 )

nervous system

open neural tube ( J:62571 )

homeostasis/metabolism

pericardial edema ( J:62571 )

Genotype
MGI:3580252

cx7

• Allelic Composition: Notch1^tm1Grid/Notch1⁺; Notch4^tm1Grid/Notch4^tm1Grid
• Genetic Background: involves: 129S1/Sv * C57BL/6

growth/size/body

postnatal growth retardation ( J:62571 )

• normal size at birth but weight was only about 80% that of controls at 3 weeks of age

Genotype
MGI:3580251

cx8

• Allelic Composition: Notch1^tm1Grid/Notch1^tm1Grid; Notch2^tm1Grid/Notch2^tm1Grid
• Genetic Background: involves: 129S1/Sv * C57BL/6J

cardiovascular system

abnormal direction of heart looping ( J:83358 )

• reversed and ventral loops

embryo

abnormal left-right axis patterning ( J:83358 )

• reversed axial rotation

Genotype
MGI:3039488

cx9

• Allelic Composition: Tle5^tm1Grid/Tle5^tm1Grid; Notch1^tm1Grid/Notch1⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6J

growth/size/body

postnatal growth retardation ( J:29516 )

• these compound mutant mice were born in normal numbers, but showed the same degree of runting as mutant mice homozygous for an Aes null allele

Genotype
MGI:2687026

cx10

• Allelic Composition: Notch1^tm1Grid/Notch1^tm1Grid; Notch3^tm1Grid/Notch3^tm1Grid
• Genetic Background: Not Specified

embryo

abnormal embryo development ( J:87272 )

• fetuses observed at E9.5 exhibited defects characteristic of Notch1^tm1Grid homozygotes

• synergistic effects were not observed

abnormal developmental patterning ( J:87272 )

embryonic growth retardation ( J:87272 )

abnormal embryonic tissue morphology ( J:87272 )

growth/size/body

embryonic growth retardation ( J:87272 )