Phenotypes associated with this allele

• Allele Symbol: Nfatc3^tm1Glm
• Allele Name: targeted mutation 1, Laurie H Glimcher
• Allele ID: MGI:2182778
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nfatc3^tm1Glm/Nfatc3^tm1Glm	involves: 129S2/SvPas	MGI:3525154
cx2	Nfatc3^tm1Glm/Nfatc3^tm1Glm Nfatc4^tm1Grc/Nfatc4^tm1Grc	involves: 129S2/SvPas	MGI:3525158
cx3	Nfatc2^tm1Glm/Nfatc2^tm1Glm Nfatc3^tm1Glm/Nfatc3^tm1Glm	involves: 129S2/SvPas	MGI:3525157
cx4	Nfatc2^tm1Glm/Nfatc2^tm1Glm Nfatc3^tm1Glm/Nfatc3^tm1Glm Nfatc4^tm1Grc/Nfatc4^tm1Grc	involves: 129S2/SvPas	MGI:3525159
cx5	Nfatc3^tm1Glm/Nfatc3^tm1Glm Nfatc4^tm1Jmk/Nfatc4^tm1Jmk	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:3836581
cx6	Nfatc3^tm1Glm/Nfatc3^tm1Glm Nfatc4^tm1Jmk/Nfatc4^tm1Jmk Tg(TIE2-lacZ)182Sato/?	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:3836582
cx7	Nfatc3^tm1Glm/Nfatc3^tm1Glm Nfatc4^tm1Jmk/Nfatc4^tm1Jmk Tg(Myh6-NFATC4)#Eno/?	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6 * FVB	MGI:3836583
cx8	Nfatc3^tm1Glm/Nfatc3^tm1Glm Tg(DO11.10)10Dlo/?	involves: 129S2/SvPas * BALB/c * C3H * C57BL/6	MGI:3525155
cx9	Nfatc3^tm1Glm/Nfatc3^tm1Glm Tg(Myh6-Ppp3ca)37Eno/?	involves: 129S2/SvPas * FVB	MGI:3525156

Genotype
MGI:3525154

hm1

• Allelic Composition: Nfatc3^tm1Glm/Nfatc3^tm1Glm
• Genetic Background: involves: 129S2/SvPas

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

mortality/aging

prenatal lethality, incomplete penetrance ( J:50124 )

• homozygotes born in less than expected numbers, but survivors lived normal life spans

cardiovascular system

decreased response of heart to induced stress ( J:79608 )

• less hypertrophy after abdominal aortic banding and angiotensin II infusion

embryo

decreased embryo size ( J:50124 )

growth/size/body

periorbital edema ( J:50124 )

• some animals develop spontaneous periorbital swelling

decreased embryo size ( J:50124 )

homeostasis/metabolism

decreased response of heart to induced stress ( J:79608 )

• less hypertrophy after abdominal aortic banding and angiotensin II infusion

periorbital edema ( J:50124 )

• some animals develop spontaneous periorbital swelling

muscle

abnormal skeletal muscle morphology ( J:68675 )

decreased extensor digitorum longus weight ( J:68675 )

• muscle weight for the EDL is significantly reduced

• defect appears by E17.5

decreased soleus weight ( J:68675 )

• muscle weight for the soleus is significantly reduced

• defect appears by E17.5

decreased skeletal muscle fiber number ( J:68675 )

• fewer myofibrers than normal, affecting all types of myofibers

• defect is in primary myogenesis

muscle weakness ( J:68675 )

• isometric strength of soleus and "EDL" were significantly decreased

limbs/digits/tail

decreased extensor digitorum longus weight ( J:68675 )

• muscle weight for the EDL is significantly reduced

• defect appears by E17.5

decreased soleus weight ( J:68675 )

• muscle weight for the soleus is significantly reduced

• defect appears by E17.5

craniofacial

periorbital edema ( J:50124 )

• some animals develop spontaneous periorbital swelling

Genotype
MGI:3525158

cx2

• Allelic Composition: Nfatc3^tm1Glm/Nfatc3^tm1Glm; Nfatc4^tm1Grc/Nfatc4^tm1Grc
• Genetic Background: involves: 129S2/SvPas

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:70266 )

• 98% of homozygotes had died by E11.5

embryo

abnormal placental labyrinth vasculature morphology ( J:109139 )

• decreased vascularization at E10.5

abnormal vitelline vasculature morphology ( J:70266 )

• lack of organized blood vessels in yolk sac at E9.5

cardiovascular system

abnormal blood vessel morphology ( J:70266 )

• vascular disorganization increased from E9.5 to E10.5

• branches of internal carotids failed to form

• association of smooth muscle to endothelium is defective in both arteries and veins

abnormal intersomitic vessel morphology ( J:70266 )

• poorly formed intersomitic vessels

abnormal placental labyrinth vasculature morphology ( J:109139 )

• decreased vascularization at E10.5

abnormal vitelline vasculature morphology ( J:70266 )

• lack of organized blood vessels in yolk sac at E9.5

abnormal heart morphology ( J:84138 )

• 50% reduction in myocardial proliferation

• abnormal mitochondria in ventricular myocardium

trabecula carnea hypoplasia ( J:84138 )

• ventricular trabeculae were thin at E10.5

enlarged heart ( J:84138 )

• defects in cardiac development at E10.5 included dilated, thin translucent hearts, pericardial effusion and anemia

enlarged pericardium ( J:70266 )

• enlarged pericardial sac by E9.5

muscle

trabecula carnea hypoplasia ( J:84138 )

• ventricular trabeculae were thin at E10.5

nervous system

abnormal sensory neuron innervation pattern ( J:83744 )

• defects in sensory axon projections found in 70% of double mutants

digestive/alimentary system

aganglionic megacolon ( J:109139 )

endocrine/exocrine glands

annular pancreas ( J:109139 )

growth/size/body

enlarged heart ( J:84138 )

• defects in cardiac development at E10.5 included dilated, thin translucent hearts, pericardial effusion and anemia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Down syndrome		DOID:14250	OMIM:190685	J:109139

Genotype
MGI:3525157

cx3

• Allelic Composition: Nfatc2^tm1Glm/Nfatc2^tm1Glm; Nfatc3^tm1Glm/Nfatc3^tm1Glm
• Genetic Background: involves: 129S2/SvPas

growth/size/body

postnatal growth retardation ( J:51339 )

• modest

enlarged spleen ( J:51339 )

• massive splenomegaly by 7 weeks of age

• normal architecture is disrupted

• increased numbers of mast cells and eosinophiles

• spontaneous proliferation of splenocytes

hematopoietic system

enlarged spleen ( J:51339 )

• massive splenomegaly by 7 weeks of age

• normal architecture is disrupted

• increased numbers of mast cells and eosinophiles

• spontaneous proliferation of splenocytes

abnormal lymphocyte cell number ( J:51339 )

increased B cell number ( J:51339 )

• increased percentage of B220+ cells in lymph nodes

decreased T cell number ( J:51339 )

• decreased numbers of CD3+ T cells in lymph nodes

• decreased ratio of double positive T cells in lymph nodes

increased T cell number ( J:51339 )

• increased percentage of memory activated T cells in periphery

• increased proportion of double positive T cells in spleen

immune system

enlarged spleen ( J:51339 )

• massive splenomegaly by 7 weeks of age

• normal architecture is disrupted

• increased numbers of mast cells and eosinophiles

• spontaneous proliferation of splenocytes

abnormal lymphocyte cell number ( J:51339 )

increased B cell number ( J:51339 )

• increased percentage of B220+ cells in lymph nodes

decreased T cell number ( J:51339 )

• decreased numbers of CD3+ T cells in lymph nodes

• decreased ratio of double positive T cells in lymph nodes

increased T cell number ( J:51339 )

• increased percentage of memory activated T cells in periphery

• increased proportion of double positive T cells in spleen

abnormal lymph node morphology ( J:51339 )

• lymph node cells increased 2-3 fold

• increased numbers of eosinophiles

increased inflammatory response ( J:51339 )

blepharitis ( J:51339 )

• bilateral blepharitis by for weeks of age

• eyelids with edema and marked inflammatory infiltrates

interstitial pneumonia ( J:51339 )

• inflammatory infiltrate containing lymphocytes, macrophage, neutrophiles, and mast cells

respiratory system

interstitial pneumonia ( J:51339 )

• inflammatory infiltrate containing lymphocytes, macrophage, neutrophiles, and mast cells

vision/eye

blepharitis ( J:51339 )

• bilateral blepharitis by for weeks of age

• eyelids with edema and marked inflammatory infiltrates

Genotype
MGI:3525159

cx4

• Allelic Composition: Nfatc2^tm1Glm/Nfatc2^tm1Glm; Nfatc3^tm1Glm/Nfatc3^tm1Glm; Nfatc4^tm1Grc/Nfatc4^tm1Grc
• Genetic Background: involves: 129S2/SvPas

embryo

decreased embryo size ( J:83744 )

• smaller than stage matched controls

• stages were not delayed

growth/size/body

decreased embryo size ( J:83744 )

• smaller than stage matched controls

• stages were not delayed

nervous system

abnormal sensory neuron innervation pattern ( J:83744 )

• commissural axon growth is disrupted

• defects in sensory axon projections found in 100% of triple mutants

• spinal sensory neurons failed to project longitudinally

abnormal trigeminal nerve morphology ( J:83744 )

• trigeminal axons stunted at E10.5

abnormal spinal cord dorsal column morphology ( J:83744 )

• dorsal funiculus absent or fragmented

behavior/neurological

decreased anxiety-related response ( J:109139 )

decreased grip strength ( J:109139 )

• mutants display decreased grip strength compared to controls

abnormal locomotor activation ( J:109139 )

• mice show increased locomotor activity compared to BALB/c controls

abnormal social/conspecific interaction behavior ( J:109139 )

• mutants show increased social interaction

muscle

hypotonia ( J:109139 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Down syndrome		DOID:14250	OMIM:190685	J:109139

Genotype
MGI:3836581

cx5

• Allelic Composition: Nfatc3^tm1Glm/Nfatc3^tm1Glm; Nfatc4^tm1Jmk/Nfatc4^tm1Jmk
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:84138 )

• embryos either necrotic or resorbed at E11.5

• no live embryos after E11.5

cardiovascular system

abnormal heart morphology ( J:84138 )

• thin and translucent at E10.5

• pericardial effusions

abnormal myocardium layer morphology ( J:84138 )

• more than 50% reduction in proliferation at E10.5

• no apoptosis

abnormal myocardial fiber mitochondrial morphology ( J:84138 )

• restricted to mitochondria in the heart

• ventricular myocardium with enlarged and disorganized mitochondria

• defects in cristae formation, fewer in number or absent

• ventricular mitochondria with dilated tubules or onion-like swirls

abnormal myocardium compact layer morphology ( J:84138 )

• more than 50% reduction in the number of cells

abnormal heart development ( J:84138 )

• defects in cardiac development at E10.5

abnormal heart ventricle morphology ( J:84138 )

• ventricular myocardium with enlarged and disorganized mitochondria

• defects in cristae formation, fewer in number or absent

• ventricular mitochondria with dilated tubules or onion-like swirls

abnormal trabecula carnea morphology ( J:84138 )

• thinner

• fewer in number

dilated heart ( J:84138 )

• at E10.5

abnormal cardiovascular system physiology ( J:84138 )

• 30% reduction in mitochondrial respiration

cellular

abnormal myocardial fiber mitochondrial morphology ( J:84138 )

• restricted to mitochondria in the heart

• ventricular myocardium with enlarged and disorganized mitochondria

• defects in cristae formation, fewer in number or absent

• ventricular mitochondria with dilated tubules or onion-like swirls

abnormal cellular respiration ( J:84138 )

• 30% reduction in mitochondrial respiration

hematopoietic system

anemia ( J:84138 )

• at E10.5

embryo

embryonic growth retardation ( J:84138 )

• mild generalized developmental delay at E10.5

• head, tail and limb buds normal at E10.5

growth/size/body

embryonic growth retardation ( J:84138 )

• mild generalized developmental delay at E10.5

• head, tail and limb buds normal at E10.5

muscle

abnormal myocardium layer morphology ( J:84138 )

• more than 50% reduction in proliferation at E10.5

• no apoptosis

abnormal myocardial fiber mitochondrial morphology ( J:84138 )

• restricted to mitochondria in the heart

• ventricular myocardium with enlarged and disorganized mitochondria

• defects in cristae formation, fewer in number or absent

• ventricular mitochondria with dilated tubules or onion-like swirls

abnormal trabecula carnea morphology ( J:84138 )

• thinner

• fewer in number

abnormal myocardium compact layer morphology ( J:84138 )

• more than 50% reduction in the number of cells

Genotype
MGI:3836582

cx6

• Allelic Composition: Nfatc3^tm1Glm/Nfatc3^tm1Glm; Nfatc4^tm1Jmk/Nfatc4^tm1Jmk; Tg(TIE2-lacZ)182Sato/?
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal dorsal aorta morphology ( J:84138 )

• reduced number of smooth muscle cells in the dorsal aorta but no hemorrhage

Genotype
MGI:3836583

cx7

• Allelic Composition: Nfatc3^tm1Glm/Nfatc3^tm1Glm; Nfatc4^tm1Jmk/Nfatc4^tm1Jmk; Tg(Myh6-NFATC4)#Eno/?
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6 * FVB

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:84138 )

• viability extended to around E12

• no live embryos at E12.5 or later

cardiovascular system

cardiovascular system phenotype ( J:84138 )

N • normal heart phenotype at E11.5

N • heart mitochondrial respiration normal at E10.5

N • 70% of mitochondria are normal in heart muscle at E10.5

Genotype
MGI:3525155

cx8

• Allelic Composition: Nfatc3^tm1Glm/Nfatc3^tm1Glm; Tg(DO11.10)10Dlo/?
• Genetic Background: involves: 129S2/SvPas * BALB/c * C3H * C57BL/6

hematopoietic system

small thymus ( J:50124 )

• size reduced 3 fold

increased double-negative T cell number ( J:50124 )

decreased double-positive T cell number ( J:50124 )

• increased apoptosis of double positive cells

immune system

small thymus ( J:50124 )

• size reduced 3 fold

increased double-negative T cell number ( J:50124 )

decreased double-positive T cell number ( J:50124 )

• increased apoptosis of double positive cells

endocrine/exocrine glands

small thymus ( J:50124 )

• size reduced 3 fold

Genotype
MGI:3525156

cx9

• Allelic Composition: Nfatc3^tm1Glm/Nfatc3^tm1Glm; Tg(Myh6-Ppp3ca)37Eno/?
• Genetic Background: involves: 129S2/SvPas * FVB

cardiovascular system

cardiac hypertrophy ( J:79608 )

• hypertrophy induced by the transgene was reduced

growth/size/body

cardiac hypertrophy ( J:79608 )

• hypertrophy induced by the transgene was reduced