Phenotypes associated with this allele

• Allele Symbol: Mapk1^tm1Gela
• Allele Name: targeted mutation 1, Gary E Landreth
• Allele ID: MGI:3803954
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Mapk1^tm1Gela/Mapk1^tm1Gela Osr2^tm2(cre)Jian/Osr2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5902465
cn2	Mapk1^tm1Gela/Mapk1^tm1Gela H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J * CBA/J	MGI:5902457
cn3	Mapk1^tm1Gela/Mapk1^tm1Gela Mapk3^tm1Gela/Mapk3^tm1Gela H2az2^Tg(Wnt1-cre)11Rth/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J	MGI:5660197
cn4	Mapk1^tm1Gela/Mapk1^tm1Gela H2az2^Tg(Wnt1-cre)11Rth/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J	MGI:5660194
cn5	Mapk1^tm1Gela/Mapk1^tm1Gela Mapk3^tm1Gela/Mapk3^+ H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J	MGI:5660196
cn6	Mapk1^tm1Gela/Mapk1^tm1Gela Tg(GFAP-cre)25Mes/0	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:3805515

Genotype
MGI:5902465

cn1

• Allelic Composition: Mapk1^tm1Gela/Mapk1^tm1Gela; Osr2^tm2(cre)Jian/Osr2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

craniofacial

craniofacial phenotype ( J:239772 )

N • newborns do not exhibit cleft palate and tongues and mandibles are unaffected

Genotype
MGI:5902457

cn2

• Allelic Composition: Mapk1^tm1Gela/Mapk1^tm1Gela; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6J * CBA/J

mortality/aging

neonatal lethality, complete penetrance ( J:239772 )

• mice die at birth

craniofacial

abnormal Meckel's cartilage morphology ( J:239772 )

• morphology of Meckel's cartilage is disrupted at E14.5, with a reduction in size and a complete discontinuity on one side

small Meckel's cartilage ( J:239772 )

• small at E14.5

abnormal mandible morphology ( J:239772 )

• mandibular asymmetry in newborns, with the proximal region severely affected and the distal region only mildly affected; this asymmetry is associated with the asymmetry of tongue and the elevation of a single palatal shelf

• in newborns, the more severely affected side of the mandible corresponds to the side lacking palatal shelf elevation

• marker analysis indicates an initial decrease in the pool of osteogenic progenitors in the mandible followed by a delay in the osteogenic process

• however, cell proliferation and survival in mandibles at E12.5-E15.5 is similar to controls

abnormal mandibular angle morphology ( J:239772 )

• the angle is severely disrupted or completely absent in some mice

small mandibular condyloid process ( J:239772 )

• condyle is greatly reduced in size

abnormal mandibular coronoid process morphology ( J:239772 )

• the coronoid process is severely disrupted or completely absent in some mice

small mandible ( J:239772 )

• newborn mandibles show an approximate 50% reduction in mandibular volume

maxilla hypoplasia ( J:239772 )

micrognathia ( J:239772 )

• micrognathia is detectable by E13.5 and mandibular defects are more severe at E14.5

• when micrognathia affects both sides equally, the tongue is symmetrically positioned in a high location and neither palatal shelf is elevated

failure of palatal shelf elevation ( J:239772 )

• palatal shelf elevation is impaired; both anterior and posterior regions of the palate are affected

• elevation defect is seen along the AP axis at E14.5 and E15.5

• in a rotational culture system, palatal shelves (dissected away from the mandible and tongue) from E13.5 mutants are able to elevate but do not fuse, suggesting that palatal shelf elevation defect results from primary malformation in the tongue and/or mandible

complete cleft palate ( J:239772 )

• complete cleft palate

abnormal tongue morphology ( J:239772 )

• tongues exhibit malposition and disruption of muscle patterning with absence of tendon development

• cell survival in the tongue and cell proliferation in muscular and neural crest-derived components of the tongue are not affected at E12.5-E14.5 and marker analysis indicates that muscle differentiation in the tongue is not affected

abnormal tongue muscle morphology ( J:239772 )

• the organization of fibers in both the intrinsic and extrinsic muscles of the tongue is altered, resulting in gross disruption of the muscle pattern and position

abnormal extrinsic tongue muscle morphology ( J:239772 )

• at E15.5, the extrinsic muscles of the tongue are attached directly to the Meckel's cartilage and in close vicinity to the bone primordium compared to control muscles which are not in contact with the cartilage or the osteogenic progenitors

abnormal tongue position ( J:239772 )

• tongues exhibit malposition: typically, one side of the tongue descends whereas the other side remains high, blocking the elevation of one palatal shelf

decreased tongue size ( J:239772 )

• approximate 45% reduction in tongue volume

digestive/alimentary system

failure of palatal shelf elevation ( J:239772 )

• palatal shelf elevation is impaired; both anterior and posterior regions of the palate are affected

• elevation defect is seen along the AP axis at E14.5 and E15.5

• in a rotational culture system, palatal shelves (dissected away from the mandible and tongue) from E13.5 mutants are able to elevate but do not fuse, suggesting that palatal shelf elevation defect results from primary malformation in the tongue and/or mandible

complete cleft palate ( J:239772 )

• complete cleft palate

abnormal tongue morphology ( J:239772 )

• tongues exhibit malposition and disruption of muscle patterning with absence of tendon development

• cell survival in the tongue and cell proliferation in muscular and neural crest-derived components of the tongue are not affected at E12.5-E14.5 and marker analysis indicates that muscle differentiation in the tongue is not affected

abnormal tongue muscle morphology ( J:239772 )

• the organization of fibers in both the intrinsic and extrinsic muscles of the tongue is altered, resulting in gross disruption of the muscle pattern and position

abnormal extrinsic tongue muscle morphology ( J:239772 )

• at E15.5, the extrinsic muscles of the tongue are attached directly to the Meckel's cartilage and in close vicinity to the bone primordium compared to control muscles which are not in contact with the cartilage or the osteogenic progenitors

abnormal tongue position ( J:239772 )

• tongues exhibit malposition: typically, one side of the tongue descends whereas the other side remains high, blocking the elevation of one palatal shelf

decreased tongue size ( J:239772 )

• approximate 45% reduction in tongue volume

growth/size/body

failure of palatal shelf elevation ( J:239772 )

• palatal shelf elevation is impaired; both anterior and posterior regions of the palate are affected

• elevation defect is seen along the AP axis at E14.5 and E15.5

• in a rotational culture system, palatal shelves (dissected away from the mandible and tongue) from E13.5 mutants are able to elevate but do not fuse, suggesting that palatal shelf elevation defect results from primary malformation in the tongue and/or mandible

complete cleft palate ( J:239772 )

• complete cleft palate

abnormal tongue morphology ( J:239772 )

• tongues exhibit malposition and disruption of muscle patterning with absence of tendon development

• cell survival in the tongue and cell proliferation in muscular and neural crest-derived components of the tongue are not affected at E12.5-E14.5 and marker analysis indicates that muscle differentiation in the tongue is not affected

abnormal tongue muscle morphology ( J:239772 )

• the organization of fibers in both the intrinsic and extrinsic muscles of the tongue is altered, resulting in gross disruption of the muscle pattern and position

abnormal extrinsic tongue muscle morphology ( J:239772 )

• at E15.5, the extrinsic muscles of the tongue are attached directly to the Meckel's cartilage and in close vicinity to the bone primordium compared to control muscles which are not in contact with the cartilage or the osteogenic progenitors

abnormal tongue position ( J:239772 )

• tongues exhibit malposition: typically, one side of the tongue descends whereas the other side remains high, blocking the elevation of one palatal shelf

decreased tongue size ( J:239772 )

• approximate 45% reduction in tongue volume

muscle

abnormal tongue muscle morphology ( J:239772 )

• the organization of fibers in both the intrinsic and extrinsic muscles of the tongue is altered, resulting in gross disruption of the muscle pattern and position

abnormal extrinsic tongue muscle morphology ( J:239772 )

• at E15.5, the extrinsic muscles of the tongue are attached directly to the Meckel's cartilage and in close vicinity to the bone primordium compared to control muscles which are not in contact with the cartilage or the osteogenic progenitors

skeleton

abnormal Meckel's cartilage morphology ( J:239772 )

• morphology of Meckel's cartilage is disrupted at E14.5, with a reduction in size and a complete discontinuity on one side

small Meckel's cartilage ( J:239772 )

• small at E14.5

abnormal mandible morphology ( J:239772 )

• mandibular asymmetry in newborns, with the proximal region severely affected and the distal region only mildly affected; this asymmetry is associated with the asymmetry of tongue and the elevation of a single palatal shelf

• in newborns, the more severely affected side of the mandible corresponds to the side lacking palatal shelf elevation

• marker analysis indicates an initial decrease in the pool of osteogenic progenitors in the mandible followed by a delay in the osteogenic process

• however, cell proliferation and survival in mandibles at E12.5-E15.5 is similar to controls

abnormal mandibular angle morphology ( J:239772 )

• the angle is severely disrupted or completely absent in some mice

small mandibular condyloid process ( J:239772 )

• condyle is greatly reduced in size

abnormal mandibular coronoid process morphology ( J:239772 )

• the coronoid process is severely disrupted or completely absent in some mice

small mandible ( J:239772 )

• newborn mandibles show an approximate 50% reduction in mandibular volume

maxilla hypoplasia ( J:239772 )

micrognathia ( J:239772 )

• micrognathia is detectable by E13.5 and mandibular defects are more severe at E14.5

• when micrognathia affects both sides equally, the tongue is symmetrically positioned in a high location and neither palatal shelf is elevated

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Weissenbacher-Zweymuller syndrome		DOID:4258	OMIM:261800	J:239772

Genotype
MGI:5660197

cn3

• Allelic Composition: Mapk1^tm1Gela/Mapk1^tm1Gela; Mapk3^tm1Gela/Mapk3^tm1Gela; H2az2^{Tg(Wnt1-cre)11Rth}/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J

craniofacial

absent mandible ( J:144862 )

short maxilla ( J:144862 )

• more severe than in mice heterozygous for Mapk3^tm1Gela

small pharyngeal arch ( J:144862 )

• at E10.5

absent tongue ( J:144862 )

absent outer ear ( J:144862 )

growth/size/body

absent tongue ( J:144862 )

absent outer ear ( J:144862 )

decreased body length ( J:144862 )

cardiovascular system

persistent truncus arteriosus ( J:144862 )

• in 5 of 5 mice at E16.5 and E17.5

ventricular septal defect ( J:144862 )

• in 5 of 5 mice at E16.5 and E17.5

endocrine/exocrine glands

athymia ( J:144862 )

abnormal thyroid gland morphology ( J:144862 )

• singled-lobed and medially localized

digestive/alimentary system

absent tongue ( J:144862 )

embryo

small pharyngeal arch ( J:144862 )

• at E10.5

hearing/vestibular/ear

absent outer ear ( J:144862 )

hematopoietic system

athymia ( J:144862 )

immune system

athymia ( J:144862 )

skeleton

absent mandible ( J:144862 )

short maxilla ( J:144862 )

• more severe than in mice heterozygous for Mapk3^tm1Gela

vision/eye

abnormal eye distance/ position ( J:144862 )

Genotype
MGI:5660194

cn4

• Allelic Composition: Mapk1^tm1Gela/Mapk1^tm1Gela; H2az2^{Tg(Wnt1-cre)11Rth}/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:144862 )

• although present in late gestation, no viable neonates are detected

craniofacial

mandible hypoplasia ( J:144862 )

short maxilla ( J:144862 )

cleft palate ( J:144862 )

cardiovascular system

persistent truncus arteriosus ( J:144862 )

• in 1 of 5 mice at E16.5

double outlet right ventricle ( J:144862 )

• in 1 of 4 mice at E17.5

ventricular septal defect ( J:144862 )

• in 2 of 5 mice at E16.5

endocrine/exocrine glands

abnormal thymus morphology ( J:144862 )

• in 1 of 5 mice at E16.5

abnormal thyroid gland morphology ( J:144862 )

• in 1 of 5 mice at E16.5

growth/size/body

cleft palate ( J:144862 )

digestive/alimentary system

cleft palate ( J:144862 )

immune system

abnormal thymus morphology ( J:144862 )

• in 1 of 5 mice at E16.5

hematopoietic system

abnormal thymus morphology ( J:144862 )

• in 1 of 5 mice at E16.5

skeleton

mandible hypoplasia ( J:144862 )

short maxilla ( J:144862 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
velocardiofacial syndrome		DOID:12583	OMIM:192430	J:144862

Genotype
MGI:5660196

cn5

• Allelic Composition: Mapk1^tm1Gela/Mapk1^tm1Gela; Mapk3^tm1Gela/Mapk3⁺; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J

growth/size/body

cleft palate ( J:144862 )

• more severe than in mice with normal Mapk3

absent tongue ( J:144862 )

craniofacial

mandible hypoplasia ( J:144862 )

• more severe than in mice with normal Mapk3

short maxilla ( J:144862 )

• more severe than in mice with normal Mapk3

cleft palate ( J:144862 )

• more severe than in mice with normal Mapk3

absent tongue ( J:144862 )

cardiovascular system

persistent truncus arteriosus ( J:144862 )

• in 3 of 3 mice at E16.5 and E17.5

ventricular septal defect ( J:144862 )

• in 3 of 3 mice at E16.5 and E17.5

endocrine/exocrine glands

abnormal thymus morphology ( J:144862 )

• single-lobed, fused and misplaced

abnormal thyroid gland morphology ( J:144862 )

• singled-lobed and medially localized

digestive/alimentary system

cleft palate ( J:144862 )

• more severe than in mice with normal Mapk3

absent tongue ( J:144862 )

hematopoietic system

abnormal thymus morphology ( J:144862 )

• single-lobed, fused and misplaced

immune system

abnormal thymus morphology ( J:144862 )

• single-lobed, fused and misplaced

skeleton

mandible hypoplasia ( J:144862 )

• more severe than in mice with normal Mapk3

short maxilla ( J:144862 )

• more severe than in mice with normal Mapk3

vision/eye

abnormal eye distance/ position ( J:144862 )

Genotype
MGI:3805515

cn6

• Allelic Composition: Mapk1^tm1Gela/Mapk1^tm1Gela; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

behavior/neurological

abnormal contextual conditioning behavior ( J:137882 )

• long-term memory for contextual conditioning is significantly impaired compared to wild-type controls

• overtraining does not rescue defect as mice continue to display less freezing behavior than wild-type littermates

abnormal cued conditioning behavior ( J:137882 )

• long-term memory for cued conditioning is significantly impaired compared to wild-type controls

• overtraining does not rescue defect as mice continue to display less freezing behavior than wild-type littermates

nervous system

abnormal neuron differentiation ( J:137882 )

abnormal cerebral cortex morphology ( J:137882 )

• cellular density appears greater throughout cortex, but laminar organization is normal

• at P10 mice show a 10% reduction in neuron number in cerebral cortex, with a 40% increase in non-neuronal, presumptive glial cells

• neuron number in layer VI and cortical preplate is reduced by 35%at P2

• in layer V, there are only 50% as many neurons as in wild-type at P2

• layers II-IV show a 30% decrease in neurons at P2

• dramatic increase in astrocyte number is observed throughout cortex and subventricular zone

• astrocyte metabolism and viability are similar to wild-type; neuronal apoptosis and differentiation are similar to controls

thin cerebral cortex ( J:137882 )

• cortical thickness is significantly reduced throughout the dorsal telencephalon relative to wild-type at P2

cellular

abnormal neuron differentiation ( J:137882 )