All Phenotypes Notch2<tm3Grid> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Notch2^tm3Grid
targeted mutation 3, Tom Gridley
MGI:3617328

Summary

11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Notch2^tm3Grid/Notch2^tm3.1Grid Tg(Tagln-cre)1Her/?	involves: 129 * C57BL/6	MGI:3778203
cn2	Notch2^tm3Grid/Notch2^tm3.1Grid Pax3^tm1(cre)Joe/Pax3⁺	involves: 129 * C57BL/6	MGI:3778204
cn3	Notch2^tm3Grid/Notch2^tm3Grid Foxg1^tm1(cre)Skm/Foxg1⁺	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:4361706
cn4	Notch2^tm3Grid/Notch2^tm3Grid Tg(Pax3-cre)1Joe/0	involves: 129S1/Sv	MGI:3713802
cn5	Notch2^tm3Grid/Notch2^tm3Grid Tg(Tpbpa-cre,-EGFP)5Jcc/0	involves: 129S1/Sv	MGI:5288006
cn6	Notch2^tm2Grid/Notch2^tm3Grid Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S1/Sv * C57BL/6 * DBA	MGI:3778812
cn7	Notch2^tm3Grid/Notch2^tm3.1Grid Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S1/Sv * C57BL/6 * DBA	MGI:3778811
cn8	Notch1^tm6.1Rko/Notch1⁺ Notch2^tm3Grid/Notch2^tm3Grid Tg(Pax3-cre)1Joe/0	involves: 129S1/Sv * C57BL/6 * SJL	MGI:5523681
cn9	Notch2^tm3Grid/Notch2^tm3Grid Tg(Pax3-cre)1Joe/0	involves: 129S1/Sv * C57BL/6 * SJL	MGI:5523680
cn10	Notch1^tm6.1Rko/Notch1^tm6.1Rko Notch2^tm3Grid/Notch2^tm3Grid Tg(Pax3-cre)1Joe/0	involves: 129S1/Sv * C57BL/6 * SJL	MGI:5523682
cn11	Notch1^tm1Agt/Notch1^tm1Agt Notch2^tm3Grid/Notch2^tm3Grid Tg(TcrAND)53Hed/?	involves: 129/Sv * 129S1/Sv * C57BL/6 * SJL	MGI:3720331

Allelic Composition	Notch2^tm3Grid/Notch2^tm3.1Grid Tg(Tagln-cre)1Her/?
Genetic Background	involves: 129 * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Notch2^tm3.1Grid mutation (0 available); any Notch2 mutation (97 available)
Notch2^tm3Grid mutation (2 available); any Notch2 mutation (97 available)
Tg(Tagln-cre)1Her mutation (2 available)

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:132939 )

• there is a 50% mortality rate between birth and weaning

cardiovascular system

pulmonary artery stenosis ( J:132939 )

• pulmonary arteries of E18.5 embryos and newborns are significantly smaller

aorta stenosis ( J:132939 )

• aorta diameters of all E18.5 embryos and newborns are decreased compared to wild-type mice

abnormal blood flow velocity ( J:132939 )

• mean aortic velocity in one month old mice is 1.74 m/s which is significantly faster than the mean velocity of 0.93 m/s for controls

• mean pulmonary velocity in one month old mice is 1.9 m/s which is significantly faster than the mean velocity of 1.5 m/s for controls

homeostasis/metabolism

cyanosis ( J:132939 )

• is observed in neonates

Allelic Composition	Notch2^tm3Grid/Notch2^tm3.1Grid Pax3^tm1(cre)Joe/Pax3⁺
Genetic Background	involves: 129 * C57BL/6

Find Mice

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:132939 )

• there is a 50% mortality rate between birth and weaning

cardiovascular system

pulmonary artery stenosis ( J:132939 )

• pulmonary arteries of E18.5 embryos and newborns are significantly smaller

supravalvar pulmonary trunk stenosis ( J:132939 )

• the mean inner diameter of the pulmonary trunk is 1.22 mm compared to 1.56 mm for age-matched controls

aorta stenosis ( J:132939 )

• aorta diameters of all E18.5 embryos and newborns are decreased compared to wild-type mice

• the mean aortic diameter is 1.3 mm compared to 1.5 mm for age-matched controls

abnormal vascular smooth muscle morphology ( J:132939 )

• smooth muscle cell proliferation is reduced to 9% in E16.5 embryos compared to 22.5% of wild-type embryos

craniofacial

abnormal tooth morphology ( J:132939 )

• dental malformations inhibit the ability of mice to feed postnatally

growth/size/body

abnormal tooth morphology ( J:132939 )

• dental malformations inhibit the ability of mice to feed postnatally

decreased body weight ( J:132939 )

• by one week of age, mice weigh significantly less than control littermates

homeostasis/metabolism

cyanosis ( J:132939 )

• a mild cyanotic appearance is observed in neonates

muscle

abnormal vascular smooth muscle morphology ( J:132939 )

• smooth muscle cell proliferation is reduced to 9% in E16.5 embryos compared to 22.5% of wild-type embryos

skeleton

abnormal tooth morphology ( J:132939 )

• dental malformations inhibit the ability of mice to feed postnatally

Allelic Composition	Notch2^tm3Grid/Notch2^tm3Grid Foxg1^tm1(cre)Skm/Foxg1⁺
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxg1^tm1(cre)Skm mutation (2 available); any Foxg1 mutation (28 available)
Notch2^tm3Grid mutation (2 available); any Notch2 mutation (97 available)

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

mortality/aging

premature death ( J:130929 )

• nearly two-thirds do not survive to adulthood

• born in approximately Mendelian ratios (21%)

growth/size/body

abnormal olfactory epithelium morphology ( J:130929 )

• disrupted relatively uniform spacing of sustentacular nuclei

• some areas significantly disrupted and thinner, other areas appear relatively normal

• smaller and more irregularly shaped sustentacular nuclei

• gaps and a reduction in the number of dendritic tufts at the apical surface

decreased body weight ( J:130929 )

• no apparent weight difference at P0

• weigh 27% less than controls at 2.5 week old

• weigh 47% less than controls at 8-19 week old

nervous system

small pituitary gland ( J:130929 )

• significantly smaller pituitary in size

increased neuronal precursor cell number ( J:130929 )

• increased olfactory neuronal progenitors in the neuronal and apical layer in adults mutants

abnormal sensory neuron morphology ( J:130929 )

• disorganized olfactory sensory neurons

neuron degeneration ( J:130929 )

• does not occur during early postnatal life (P0-2.5weeks), but increase as the animal ages

• increased TUNEL-positive cells in the neuronal layer of the olfactory epithelium

abnormal nervous system physiology ( J:130929 )

• lower Glutathione S-transferase activity in mutant olfactory epithelia

increased neuron apoptosis ( J:130929 )

• increased TUNEL-positive cells in the neuronal layer of the olfactory epithelium

• does not occur during early postnatal life (P0-2.5weeks), but increase as the animal ages

taste/olfaction

abnormal olfactory epithelium morphology ( J:130929 )

• disrupted relatively uniform spacing of sustentacular nuclei

• some areas significantly disrupted and thinner, other areas appear relatively normal

• smaller and more irregularly shaped sustentacular nuclei

• gaps and a reduction in the number of dendritic tufts at the apical surface

cellular

increased apoptosis ( J:130929 )

• increased TUNEL-positive cells in the apical layer of the olfactory epithelium (0.3 cells/mm vs. 0/mm)

increased neuron apoptosis ( J:130929 )

• increased TUNEL-positive cells in the neuronal layer of the olfactory epithelium

• does not occur during early postnatal life (P0-2.5weeks), but increase as the animal ages

endocrine/exocrine glands

small pituitary gland ( J:130929 )

• significantly smaller pituitary in size

respiratory system

abnormal olfactory epithelium morphology ( J:130929 )

• disrupted relatively uniform spacing of sustentacular nuclei

• some areas significantly disrupted and thinner, other areas appear relatively normal

• smaller and more irregularly shaped sustentacular nuclei

• gaps and a reduction in the number of dendritic tufts at the apical surface

craniofacial

abnormal olfactory epithelium morphology ( J:130929 )

• disrupted relatively uniform spacing of sustentacular nuclei

• some areas significantly disrupted and thinner, other areas appear relatively normal

• smaller and more irregularly shaped sustentacular nuclei

• gaps and a reduction in the number of dendritic tufts at the apical surface

Allelic Composition	Notch2^tm3Grid/Notch2^tm3Grid Tg(Pax3-cre)1Joe/0
Genetic Background	involves: 129S1/Sv

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Notch2^tm3Grid mutation (2 available); any Notch2 mutation (97 available)
Tg(Pax3-cre)1Joe mutation (0 available)

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

mortality/aging

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

• embryos die at E13.5 from vascular failure and hemorrhage into internal organs

renal/urinary system

abnormal kidney vasculature morphology ( J:119907 )

• on P2, kidneys appear to have lost vascular integrity

kidney hemorrhage ( J:119907 )

• hemorrhage into interstitial spaces of kidneys is observed at P1

abnormal kidney collecting duct morphology ( J:119907 )

• collecting ducts are less extensively branched than in wild-type or heterozygous littermates at P2

absent podocytes ( J:119907 )

• do not develop

abnormal renal glomerulus morphology ( J:119907 )

abnormal kidney development ( J:119907 )

• convoluted renal epithelia is not distinguishable from glomeruli or S-shaped bodies at P2 in developing kidneys

• kidneys develop lacking proximal tubule and podocytes

• mice lack filtration apparatus, which results in fatal renal failure within 48 hours of birth

abnormal kidney pelvis morphology ( J:119907 )

abnormal kidney papilla morphology ( J:119907 )

• papilla is flattened at P2

small kidney ( J:119907 )

• kidneys of newborns are smaller than heterozygous Notch2 littermates

renal hypoplasia ( J:119907 )

• kidneys are hypoplastic at P2

abnormal renal tubule morphology ( J:119907 )

abnormal proximal convoluted tubule morphology ( J:119907 )

• tubule does not develop

abnormal urinary bladder morphology ( J:119907 )

• animals have small bladders compared to littermates

kidney failure ( J:119907 )

• fatal renal failure within 48 hours of birth

cardiovascular system

abnormal kidney vasculature morphology ( J:119907 )

• on P2, kidneys appear to have lost vascular integrity

kidney hemorrhage ( J:119907 )

• hemorrhage into interstitial spaces of kidneys is observed at P1

cellular

cellular phenotype ( J:119907 )

N	• no significant differences are seen in apoptosis or numbers of proliferating cells in renal epithelia close to ureteric bud tips in mutants relative to controls

abnormal cell cycle ( J:119907 )

• in mutant kidneys, subpopulation of Notch2-deficient, Pax2^high, Jag-expressing cells enter cell cycle ~2-fold less frequently than cells in wild-type

Allelic Composition	Notch2^tm3Grid/Notch2^tm3Grid Tg(Tpbpa-cre,-EGFP)5Jcc/0
Genetic Background	involves: 129S1/Sv

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Notch2^tm3Grid mutation (2 available); any Notch2 mutation (97 available)
Tg(Tpbpa-cre,-EGFP)5Jcc mutation (4 available)

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

cardiovascular system

abnormal placenta vasculature ( J:173527 )

• trophoblast giant cells and glycogen trophoblast cells fail to invade maternal spiral arterioles at E12.5 indicating a failure of endovascular invasion

• trophoblast-lined canals in the placenta that transport maternal blood to the labyrinth are reduced in size by 30-40%

• placentas fail to remodel maternal blood vessels adequately resulting in reduced placental perfusion by about 23% in mutants

ovary hemorrhage ( J:173527 )

embryo

abnormal placenta vasculature ( J:173527 )

• trophoblast giant cells and glycogen trophoblast cells fail to invade maternal spiral arterioles at E12.5 indicating a failure of endovascular invasion

• trophoblast-lined canals in the placenta that transport maternal blood to the labyrinth are reduced in size by 30-40%

• placentas fail to remodel maternal blood vessels adequately resulting in reduced placental perfusion by about 23% in mutants

endocrine/exocrine glands

ovary hemorrhage ( J:173527 )

abnormal ovary morphology ( J:173527 )

• females exhibit severe ovarian defects

ovarian follicular cyst ( J:173527 )

reproductive system

ovary hemorrhage ( J:173527 )

abnormal ovary morphology ( J:173527 )

• females exhibit severe ovarian defects

ovarian follicular cyst ( J:173527 )

abnormal pregnancy ( J:173527 )

• homozygous mothers mated with homozygous males exhibit a loss of embryos as early as E9.5, with 54% resorption between E11.5 and E14.5

• homozygous mothers mated with heterozygous males and heterozygous mothers mated with homozygous males exhibit a similar loss of both heterozygous and homozygous embryos, indicating that lethality is not due to maternal factors and is correlated with the presence of homozygous embryos rather than the genotype of individual embryos

• homozygous mothers have fewer implantation sites than controls

growth/size/body

ovarian follicular cyst ( J:173527 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pre-eclampsia		DOID:10591	OMIM:189800 OMIM:609402 OMIM:609403 OMIM:609404 OMIM:614592	J:173527

Allelic Composition	Notch2^tm2Grid/Notch2^tm3Grid Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S1/Sv * C57BL/6 * DBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Notch2^tm2Grid mutation (0 available); any Notch2 mutation (97 available)
Notch2^tm3Grid mutation (2 available); any Notch2 mutation (97 available)
Speer6-ps1^{Tg(Alb-cre)21Mgn} mutation (6 available); any Speer6-ps1 mutation (4 available)

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

liver/biliary system

focal hepatic necrosis ( J:133171 )

abnormal bile duct morphology ( J:133171 )

• by P7 few bile ducts are present

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:133171 )

N	• blood urea nitrogen levels are normal

increased circulating bilirubin level ( J:133171 )

• in some mice

increased circulating alanine transaminase level ( J:133171 )

• in some mice

increased circulating alkaline phosphatase level ( J:133171 )

• in some mice

growth/size/body

decreased body size ( J:133171 )

decreased body weight ( J:133171 )

• at 4 to 5 weeks of age, mice are 15% lighter than wild-type

• at P8 to P9, mice are 19% lighter than wild-type

endocrine/exocrine glands

abnormal bile duct morphology ( J:133171 )

• by P7 few bile ducts are present

cellular

focal hepatic necrosis ( J:133171 )

Allelic Composition	Notch2^tm3Grid/Notch2^tm3.1Grid Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S1/Sv * C57BL/6 * DBA

Find Mice

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

liver/biliary system

focal hepatic necrosis ( J:133171 )

abnormal bile duct morphology ( J:133171 )

• by P7 few bile ducts are present

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:133171 )

N	• blood urea nitrogen levels are normal

increased circulating bilirubin level ( J:133171 )

• in some mice

increased circulating alanine transaminase level ( J:133171 )

• in some mice

increased circulating alkaline phosphatase level ( J:133171 )

• in some mice

growth/size/body

decreased body size ( J:133171 )

decreased body weight ( J:133171 )

• at P8 to P9, mice are 19% lighter than wild-type

• at 4 to 5 weeks of age, mice are 15% lighter than wild-type

endocrine/exocrine glands

abnormal bile duct morphology ( J:133171 )

• by P7 few bile ducts are present

cellular

focal hepatic necrosis ( J:133171 )

Allelic Composition	Notch1^tm6.1Rko/Notch1⁺ Notch2^tm3Grid/Notch2^tm3Grid Tg(Pax3-cre)1Joe/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Notch1^tm6.1Rko mutation (0 available); any Notch1 mutation (115 available)
Notch2^tm3Grid mutation (2 available); any Notch2 mutation (97 available)
Tg(Pax3-cre)1Joe mutation (0 available)

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

renal/urinary system

renal hypoplasia ( J:198632 )

• newborns have hypoplastic kidneys without functional nephrons; one copy of the N2ICD expressed from the Notch1 locus cannot rescue nephrons

Allelic Composition	Notch2^tm3Grid/Notch2^tm3Grid Tg(Pax3-cre)1Joe/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Notch2^tm3Grid mutation (2 available); any Notch2 mutation (97 available)
Tg(Pax3-cre)1Joe mutation (0 available)

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

mortality/aging

neonatal lethality, complete penetrance ( J:198632 )

• pups die within 24 hours of birth

renal/urinary system

renal hypoplasia ( J:198632 )

Allelic Composition	Notch1^tm6.1Rko/Notch1^tm6.1Rko Notch2^tm3Grid/Notch2^tm3Grid Tg(Pax3-cre)1Joe/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * SJL

Find Mice

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

mortality/aging

neonatal lethality, complete penetrance ( J:198632 )

• pups die within 24 hours of birth

renal/urinary system

renal hypoplasia ( J:198632 )

• newborns have hypoplastic kidneys without functional nephrons; two copies of the Notch1 intracellular domain (N1ICD) expressed from the Notch2 locus cannot rescue nephrons

Allelic Composition	Notch1^tm1Agt/Notch1^tm1Agt Notch2^tm3Grid/Notch2^tm3Grid Tg(TcrAND)53Hed/?
Genetic Background	involves: 129/Sv * 129S1/Sv * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Notch1^tm1Agt mutation (0 available); any Notch1 mutation (115 available)
Notch2^tm3Grid mutation (2 available); any Notch2 mutation (97 available)
Tg(TcrAND)53Hed mutation (2 available)

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

immune system

abnormal humoral immune response ( J:123631 )

• the immune response to strong T helper2 inducing conditions is absent

decreased interleukin-4 secretion ( J:123631 )

• after 5 days of culture of antigen presenting cells with Schistosoma mansoni soluble egg antigen and pigeon cytochrome C, no IL-4 is produced as it is in wild-type cells

abnormal response to infection ( J:123631 )

• after 5 days of culture of antigen presenting cells with Schistosoma mansoni soluble egg antigen and pigeon cytochrome C, no IL-4 is produced as it is in wild-type cells

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