Overview

Also Known As:AP-2 -

These Tcfap2a knock-out mice exhibit embryonic lethality with multiple severe developmental defects of the face, skull, sensory organs, and cranial ganglia.

Donating Investigator

Rudolf Jaenisch, Whitehead Institute, Massachusetts Institute of Technology

Genetic overview

Genetic Background	Generation

Tfap2a^tm1Jae

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Tfap2a	transcription factor AP-2, alpha

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Research Applications

Cancer Research
Developmental Biology Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Tcfap2a^tm1Jae mutation die around embryonic day 9.0-9.5 due to failure of cranial closure. These embryos also show multiple severe developmental defects of the face, skull, sensory organs, and cranial ganglia. There is increased apoptosis in the midbrain of day 9 embryos, coinciding with failure of cranial closure.

Development

This strain was developed in the laboratory of Dr. Rudolf Jaenisch at the Massachusetts Institute of Technology. Exon 5 of the Tcfap2a gene was replaced with a vector containing the neo resistance gene. The 129-derived J1 ES cell line was used. Mice have been backcrossed to BALB/c mice.

Control Suggestions

Wild-type from the colony
000651 BALB/cJ

Additional Information

Considerations for Choosing Controls

Selected References

Schorle H; Meier P; Buchert M; Jaenisch R; Mitchell PJ. 1996. Transcription factor AP-2 essential for cranial closure and craniofacial development. Nature 381(6579):235-8PubMed: 8622765 MGI: J:33032

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Genetics

Tfap2a^tm1Jae

Allele Symbol: Tfap2a^tm1Jae

Allele Name	targeted mutation 1, Rudolf Jaenisch
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	AP-2 -
Gene Symbol and Name	Tfap2a, transcription factor AP-2, alpha
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	13
Molecular Note	A neomycin resistance cassette replaced a genomic fragment containing exon 5, which encodes part of the DNA binding domain of the protein.
Mutations Made By	Rudolf Jaenisch, Whitehead Institute, Massachusetts Institute of Technology

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Tfap2a^tm1Jae related

Cancer Research
- Genes Regulating Growth and Proliferation
Developmental Biology Research
- Neurodevelopmental Defects
Neurobiology Research
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Tfap2a^tm1Jae/Tfap2a^tm1Jae
either: (involves: 129S4/SvJae) or (involves: 129S4/SvJae * BALB/c)

growth/size/body region phenotype

absent outer ear
- homozygous null mice lack external ears

midline facial cleft
- at 9.5-11.5 dpc, medial nasal and mandibular prominences fail to undergo normal midline fusions, resulting in full midline facial clefting

abnormal ventral body wall morphology
- the ventral body wall fails to close medially, allowing extrusion of thoracic and abdominal organs through the open rib cage

hearing/vestibular/ear phenotype

absent outer ear
- homozygous null mice lack external ears

limbs/digits/tail phenotype

absent radius
- homozygotes display various limb defects, such as lack of a radius bone; however, these defects are not fully penetrant

mortality/aging

perinatal lethality, complete penetrance
- homozygous null mice die perinatally

cellular phenotype

abnormal apoptosis
- failure of cranial closure at 9 dpc coincides with increased apoptosis in the midbrain, anterior hindbrain and proximal mesenchyme of the first branchial arch
- at 9.5 dpc, cell death is still elevated in the trigeminal ganglia primordia and proximal first-branchial-arch mesenchyme, but not in brain neuroepithelia

nervous system phenotype

incomplete rostral neuropore closure
- at 9-9.5 dpc, the cranial folds fail to join dorsomedially for closure, and the entire brain plate remains open thereafter
- the cranial portion of the neural tube fails to close

small trigeminal ganglion
- the cranial ganglia, especially the trigeminal ganglia, display severe hypoplasia; dorsal root ganglia are less affected

abnormal cranial ganglia morphology
- at 10.5 dpc, the cranial ganglia are severely underdeveloped (trigeminal, geniculate, vestibulocochlear and nodose) or absent (petrosal)

exencephaly
- at 9-9.5 dpc, the cranial folds fail to join dorsomedially for closure, and the entire brain plate remains open thereafter

abnormal forebrain morphology
- expansion of the everted forebrain between 9.5-11.5 dpc leads to progressive lateral displacement of the facial primordia

skeleton phenotype

abnormal axial skeleton morphology
- at 16.5 dpc, the axial skeleton is contorted and smaller relative to wild-type

acrania
- at 16.5 dpc, the head skeleton is acranic (lack of skull vault)

cranioschisis
- the two brain hemispheres develop open with the germinal layer facing outward (cranioschisis)

scoliosis
- at 16.5 dpc, homozygotes display a scoliotic spine

splayed ribs
- the ribs of homozygous null mutants splay outwards but are normal in number

abnormal cranium morphology
- homozygotes display severe dysmorphogenesis of the skull and a fully penetrant cranio-abdominoschisis
- at 16.5 dpc, all major skull bones of non-somitic origin are morphologically abnormal or severely reduced

absent sternum
- at 16.5 dpc, homozygotes display no sternum medially

absent radius
- homozygotes display various limb defects, such as lack of a radius bone; however, these defects are not fully penetrant

abnormal thoracic cage morphology
- open rib cage

vision/eye phenotype

abnormal lens vesicle development
- the contact between the optic cup and head ectoderm is lost, and lens induction is aborted
- the optic cup is displaced with dysmorphic neural and pigmented retinal layers of the eye developing medially

anophthalmia
- homozygous null mice lack eyes

craniofacial phenotype

acrania
- at 16.5 dpc, the head skeleton is acranic (lack of skull vault)

abnormal cranium morphology
- at 16.5 dpc, all major skull bones of non-somitic origin are morphologically abnormal or severely reduced
- homozygotes display severe dysmorphogenesis of the skull and a fully penetrant cranio-abdominoschisis

cranioschisis
- the two brain hemispheres develop open with the germinal layer facing outward (cranioschisis)

midline facial cleft
- at 9.5-11.5 dpc, medial nasal and mandibular prominences fail to undergo normal midline fusions, resulting in full midline facial clefting

absent outer ear
- homozygous null mice lack external ears

embryo phenotype

abnormal neural fold elevation formation
- by 8.5-9 dpc, mutant embryos show a delayed elevation of the cranial neural folds and a more widely open brain plate

incomplete rostral neuropore closure
- the cranial portion of the neural tube fails to close
- at 9-9.5 dpc, the cranial folds fail to join dorsomedially for closure, and the entire brain plate remains open thereafter

Genotype: Tfap2a^tm1Jae/Tfap2a⁺
involves: 129P/Ola * 129S4/SvJae

behavior/neurological phenotype

pup cannibalization
- exencephalic heterozygous pups are cannibalized by their mothers

embryo phenotype

open neural tube
- in the most severe cases, heterozygotes display an open neural tube from the frontonasal region to the otic vesicle, with proliferating neural tissue covering the eyes

hearing/vestibular/ear phenotype

abnormal middle ear ossicle morphology
- the cartilage and the ossicles of the middle ear are rotated but otherwise normal

mammalian phenotype

skeleton phenotype
- Normal - heterozygotes show no defects in the axial skeleton

nervous system phenotype

open neural tube
- in the most severe cases, heterozygotes display an open neural tube from the frontonasal region to the otic vesicle, with proliferating neural tissue covering the eyes

exencephaly
- at E9.5, the neural tube defects are variable, ranging from pure midbrain exencephaly to a forebrain/midbrain exencephaly
- up to 14% of heterozygotes display a failure of the cranial neural folds to close
- notably, in heterozygotes, exencephaly is not associated with increased apoptosis or hypoplastic cranial ganglia
- a subset of heterozygotes displays a midbrain exencephaly after the mutation is crossed for one generation into 129/Ola

skeleton phenotype

short maxilla

abnormal neurocranium morphology
- up to 14% of heterozygotes show abnormal formation of the bones of the cranial vault (either absent or hypoplastic)

absent interparietal bone
- in affected heterozygotes, the interparietal bone is absent

small frontal bone
- in affected heterozygotes, only a small portion of the frontal bone is present

absent nasal bone
- in the most severe cases, the nasal bone and cartilage were malformed or absent

absent parietal bone
- in affected heterozygotes, the parietal bone is absent

short mandible

small zygomatic bone
- in affected heterozygotes, the zygomatic bone is smaller relative to wild-type

abnormal cranium morphology
- up to 14% of heterozygotes exhibit a reduction in rostrocaudal dimensions of the skull

abnormal middle ear ossicle morphology
- the cartilage and the ossicles of the middle ear are rotated but otherwise normal

craniofacial phenotype

absent nasal bone
- in the most severe cases, the nasal bone and cartilage were malformed or absent

short mandible

abnormal middle ear ossicle morphology
- the cartilage and the ossicles of the middle ear are rotated but otherwise normal

absent parietal bone
- in affected heterozygotes, the parietal bone is absent

short maxilla

abnormal cranium morphology
- up to 14% of heterozygotes exhibit a reduction in rostrocaudal dimensions of the skull

small zygomatic bone
- in affected heterozygotes, the zygomatic bone is smaller relative to wild-type

abnormal neurocranium morphology
- up to 14% of heterozygotes show abnormal formation of the bones of the cranial vault (either absent or hypoplastic)

absent interparietal bone
- in affected heterozygotes, the interparietal bone is absent

small frontal bone
- in affected heterozygotes, only a small portion of the frontal bone is present

References

Schorle H; Meier P; Buchert M; Jaenisch R; Mitchell PJ. 1996. Transcription factor AP-2 essential for cranial closure and craniofacial development. Nature 381(6579):235-8PubMed: 8622765 MGI: J:33032

Additional - Tfap2a^tm1Jae related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Generic Neo
- Probe:Generic Neo
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to BALB/cJ inbred mice (Stock No. 000651). Homozygotes die between E9-E9.5.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Wild-type
- Wild-type x Heterozygote
- Inbred x Heterozygote
- Heterozygote x Inbred
Citation
When using the AP-2 - mouse strain in a publication, please cite the originating article(s) and include JAX stock #002794 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Tfap2a<tm1Jae>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:AP-2 -

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Tfap2atm1Jae

Allele Symbol: Tfap2atm1Jae

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Tfap2atm1Jae related

Mammalian Phenotype Terms by Genotype

Genotype: Tfap2atm1Jae/Tfap2atm1Jaeeither: (involves: 129S4/SvJae) or (involves: 129S4/SvJae * BALB/c)

growth/size/body region phenotype

hearing/vestibular/ear phenotype

limbs/digits/tail phenotype

mortality/aging

cellular phenotype

nervous system phenotype

skeleton phenotype

vision/eye phenotype

craniofacial phenotype

embryo phenotype

Genotype: Tfap2atm1Jae/Tfap2a+involves: 129P/Ola * 129S4/SvJae

behavior/neurological phenotype

embryo phenotype

hearing/vestibular/ear phenotype

mammalian phenotype

nervous system phenotype

skeleton phenotype

craniofacial phenotype

References

Additional - Tfap2atm1Jae related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Tfap2a^tm1Jae

Allele Symbol: Tfap2a^tm1Jae

Genotype: Tfap2a^tm1Jae related

Genotype: Tfap2a^tm1Jae/Tfap2a^tm1Jae
either: (involves: 129S4/SvJae) or (involves: 129S4/SvJae * BALB/c)

Genotype: Tfap2a^tm1Jae/Tfap2a⁺
involves: 129P/Ola * 129S4/SvJae

Additional - Tfap2a^tm1Jae related