Phenotypes associated with this allele

• Allele Symbol: Tfap2a^tm1Hsv
• Allele Name: targeted mutation 1, Henry M Sucov
• Allele ID: MGI:2183192
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tfap2a^tm1Hsv/Tfap2a^tm1Hsv	involves: 129S1/Sv * Black Swiss	MGI:5529922
cn2	Tfap2a^tm1Hsv/Tfap2a^tm2Will Tfap2c^tm1Will/Tfap2c^tm2Will Tg(Zp3-cre)3Mrt/0	involves: 129S1/Sv * FVB/N	MGI:3687952
cn3	Tfap2a^tm1Hsv/Tfap2a^tm2Will H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	Not Specified	MGI:3038354

Genotype
MGI:5529922

hm1

• Allelic Composition: Tfap2a^tm1Hsv/Tfap2a^tm1Hsv
• Genetic Background: involves: 129S1/Sv * Black Swiss

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

cardiovascular system

abnormal aortic arch development ( J:73813 )

persistent right dorsal aorta ( J:73813 )

• double outlet right ventricle associated with a right dorsal aorta defect in 1 of 10 E14.5-15.5 embryos

retroesophageal right subclavian artery ( J:73813 )

• retroesophageal right subclavian artery (RERSCA) is observed in 1 of 10 E14.5-15.5 embryos

double outlet right ventricle ( J:73813 )

• 8 out of 10 E14.5-15.5 embryos exhibit double outlet right ventricle (DORV)

• the remaining two E14.5-E15.5 embryos exhibit a more extreme a DORV described as tetralogy of Fallot

ventricular septal defect ( J:73813 )

• observed in all embryos studied

abnormal heart ventricle outflow tract morphology ( J:73813 )

pulmonary valve atresia ( J:73813 )

• complete atresia of the proximal pulmonary outflow tract is found in 1 of 10 E15.5 embryos

pulmonary valve stenosis ( J:73813 )

• extreme stenosis of the proximal pulmonary outflow tract is found in 1 of 10 E14.5 embryos

craniofacial

abnormal craniofacial development ( J:73813 )

• highly disorganized craniofacial structures observed in E15.5 embryos

embryo

open neural tube ( J:73813 )

• failure of neural tube closure by E9.5

growth/size/body

abnormal ventral body wall morphology ( J:73813 )

• failure of ventral body wall closure observed in E15.5 embryos

nervous system

open neural tube ( J:73813 )

• failure of neural tube closure by E9.5

Genotype
MGI:3687952

cn2

• Allelic Composition: Tfap2a^tm1Hsv/Tfap2a^tm2Will; Tfap2c^tm1Will/Tfap2c^tm2Will; Tg(Zp3-cre)3Mrt/0
• Genetic Background: involves: 129S1/Sv * FVB/N

mortality/aging

embryonic lethality between implantation and somite formation, incomplete penetrance ( J:113442 )

• a significant reduction in number of double-null embryos (5.5% vs 25% expected) compared to 3 other possible genotypic combinations results in earlier lethality than loss of either allele alone (~E7.5)

embryo

embryo phenotype ( J:113442 )

N • double-null embryos are found at ~expected frequencies (~25%) at E3.5; embryos are detected in both the morula (~75%) and blastocyst (~25%) stages, indicating that deficiency of both Tcfap2a and Tcfap2c does not affect the zygote prior to E3.5;

N • other genotypic combinations are all found at similar frequencies (~25%) at E7.5, indicating that loss of any combination of 3 of 4 wild-type Tcfap2a and Tcfap2c alleles allows embryo survival to ~E7.5

Genotype
MGI:3038354

cn3

• Allelic Composition: Tfap2a^tm1Hsv/Tfap2a^tm2Will; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: Not Specified

mortality/aging

neonatal lethality, incomplete penetrance ( J:88826 )

• a significant portion of mice died either immediately after or within days of birth, though some survive to weaning, most died shortly after birth due to neural tube defects and/or cleft secondary palate

• some pups exhibited anencephaly and either died or were cannibalized immediately after birth

• ~50% of mice, had a normal outward appearance, but died within the first day due to respiratory distress related to cleft secondary palate

pigmentation

belly spot ( J:88826 )

• observed on mice that survived to weaning

abnormal foot pigmentation ( J:88826 )

• white paws observed on mice that survived to weaning

abnormal tail pigmentation ( J:88826 )

• white bands observed on mice that survived to weaning

behavior/neurological

behavior/neurological phenotype ( J:88826 )

N • in spite of perturbed hearing, mice showed normal locomotive behavior

absent startle reflex ( J:88826 )

• mice did not startle when subjected to loud noise

cardiovascular system

cardiovascular system phenotype ( J:88826 )

N • no defect detected in the heart outflow tract

cellular

cellular phenotype ( J:88826 )

N • the amount of observed neural crest cell apoptosis did not exceed that which was observed in wild-type controls, in contrast to the extensive apoptosis observed in neural crest cells of Tcfap2a null mice

craniofacial

abnormal frontonasal suture morphology ( J:88826 )

• abnormal frontonasal suture lacking the degree of interdigitation observed in wild-type

• other cranial sutures appeared normal

abnormal neurocranium morphology ( J:88826 )

• while defects were not apparent in the skulls of newborns that did not exhibit anencephaly, craniofacial bone dysmorphologies arose with age

• while the upper jaw of affected mutants showed abnormal development, the morphology of the lower jaw was largely normal

wide frontal bone ( J:88826 )

• broader than those of wild-type

short frontal bone ( J:88826 )

• shorter than those of wild-type

small orbits ( J:88826 )

• abnormal development of craniofacial bones leads to restricted orbit size, conveying a small appearance of the eyes in the head

malocclusion ( J:88826 )

• while all teeth were present, the teeth of the upper jaw were misaligned, putatively due to the shortened snout

short maxilla ( J:88826 )

abnormal nasal bone morphology ( J:88826 )

broad nasal bone ( J:88826 )

short nasal bone ( J:88826 )

abnormal zygomatic bone morphology ( J:88826 )

• oblong stalked shape of zygomatic process

abnormal incus morphology ( J:88826 )

• flatter than controls

abnormal malleus morphology ( J:88826 )

• narrower across the base than the equivalent control bone and did not have a well-defined groove into which the incus normally fits

abnormal stapes morphology ( J:88826 )

• hypomorphic and only occurred as a small peg-shaped bone fragment

abnormal palatal shelf fusion at midline ( J:88826 )

• normal elevation but failed fusion of secondary palate

abnormal facial skin morphology ( J:88826 )

• snout shortening led to defects in skin integrity around the eyes and face that required euthanasia by ~2 months of age

abnormal periorbital skin morphology ( J:88826 )

• snout shortening led to defects in skin integrity around the eyes

short snout ( J:88826 )

• observed in mice that survived to weaning

• becoming more severe with age, eventually leading defects in skin integrity around the eyes and face

growth/size/body

wide frontal bone ( J:88826 )

• broader than those of wild-type

short frontal bone ( J:88826 )

• shorter than those of wild-type

malocclusion ( J:88826 )

• while all teeth were present, the teeth of the upper jaw were misaligned, putatively due to the shortened snout

short maxilla ( J:88826 )

abnormal nasal bone morphology ( J:88826 )

broad nasal bone ( J:88826 )

short nasal bone ( J:88826 )

abnormal zygomatic bone morphology ( J:88826 )

• oblong stalked shape of zygomatic process

abnormal palatal shelf fusion at midline ( J:88826 )

• normal elevation but failed fusion of secondary palate

abnormal facial skin morphology ( J:88826 )

• snout shortening led to defects in skin integrity around the eyes and face that required euthanasia by ~2 months of age

abnormal periorbital skin morphology ( J:88826 )

• snout shortening led to defects in skin integrity around the eyes

short snout ( J:88826 )

• observed in mice that survived to weaning

• becoming more severe with age, eventually leading defects in skin integrity around the eyes and face

decreased body weight ( J:88826 )

• while the weight of mice did not differ from that of wild-type at birth, those that survived to weaning weighed 26% less than controls

• failure to thrive, at least in part, is attributed to abnormal craniofacial development and consequent feeding impairment

hearing/vestibular/ear

abnormal incus morphology ( J:88826 )

• flatter than controls

abnormal malleus morphology ( J:88826 )

• narrower across the base than the equivalent control bone and did not have a well-defined groove into which the incus normally fits

abnormal stapes morphology ( J:88826 )

• hypomorphic and only occurred as a small peg-shaped bone fragment

limbs/digits/tail

abnormal tail pigmentation ( J:88826 )

• white bands observed on mice that survived to weaning

respiratory system

abnormal nasal bone morphology ( J:88826 )

broad nasal bone ( J:88826 )

short nasal bone ( J:88826 )

respiratory distress ( J:88826 )

• ~50% of mice developed respiratory distress and died within 1 day of birth

• associated with cleft secondary palate

skeleton

abnormal frontonasal suture morphology ( J:88826 )

• abnormal frontonasal suture lacking the degree of interdigitation observed in wild-type

• other cranial sutures appeared normal

abnormal neurocranium morphology ( J:88826 )

• while defects were not apparent in the skulls of newborns that did not exhibit anencephaly, craniofacial bone dysmorphologies arose with age

• while the upper jaw of affected mutants showed abnormal development, the morphology of the lower jaw was largely normal

wide frontal bone ( J:88826 )

• broader than those of wild-type

short frontal bone ( J:88826 )

• shorter than those of wild-type

small orbits ( J:88826 )

• abnormal development of craniofacial bones leads to restricted orbit size, conveying a small appearance of the eyes in the head

malocclusion ( J:88826 )

• while all teeth were present, the teeth of the upper jaw were misaligned, putatively due to the shortened snout

short maxilla ( J:88826 )

abnormal nasal bone morphology ( J:88826 )

broad nasal bone ( J:88826 )

short nasal bone ( J:88826 )

abnormal zygomatic bone morphology ( J:88826 )

• oblong stalked shape of zygomatic process

abnormal incus morphology ( J:88826 )

• flatter than controls

abnormal malleus morphology ( J:88826 )

• narrower across the base than the equivalent control bone and did not have a well-defined groove into which the incus normally fits

abnormal stapes morphology ( J:88826 )

• hypomorphic and only occurred as a small peg-shaped bone fragment

nervous system

nervous system phenotype ( J:88826 )

N • no defect detected in the cranial ganglia, in contrast to the extensive hypoplasia observed in Tcfap2a null mice

incomplete rostral neuropore closure ( J:88826 )

• occasional embryos exhibited severe neural tube defects affecting the entire cranial region - similar to what is observed in Tcfap2a null mice

open neural tube ( J:88826 )

• confined to the cranial neural tube and not observed affecting the trunk neural tube

anencephaly ( J:88826 )

• incomplete penetrance, observed in 15-20% of mice leading to death immediately after birth

exencephaly ( J:88826 )

• incomplete penetrance, observed in ~15% of mice

digestive/alimentary system

abnormal palatal shelf fusion at midline ( J:88826 )

• normal elevation but failed fusion of secondary palate

embryo

incomplete rostral neuropore closure ( J:88826 )

• occasional embryos exhibited severe neural tube defects affecting the entire cranial region - similar to what is observed in Tcfap2a null mice

open neural tube ( J:88826 )

• confined to the cranial neural tube and not observed affecting the trunk neural tube

vision/eye

small orbits ( J:88826 )

• abnormal development of craniofacial bones leads to restricted orbit size, conveying a small appearance of the eyes in the head

integument

abnormal facial skin morphology ( J:88826 )

• snout shortening led to defects in skin integrity around the eyes and face that required euthanasia by ~2 months of age

abnormal periorbital skin morphology ( J:88826 )

• snout shortening led to defects in skin integrity around the eyes

belly spot ( J:88826 )

• observed on mice that survived to weaning

abnormal foot pigmentation ( J:88826 )

• white paws observed on mice that survived to weaning

abnormal tail pigmentation ( J:88826 )

• white bands observed on mice that survived to weaning