Overview

Also Known As: AP-2CRE, Creface^T

These Creface transgenic mice have a cre-recombinase sequence driven by the human transcription factor AP-2, alpha promoter/enhancer elements, and a polyadenylation sequence followed by parts of exons 5-6 of Tfap2a, encoding the frontonasal prominence (FNP) and limb enhancer elements. This transgene integrated into intron 9 of the hedgehog acyltransferase (Hhat) gene, abolishing Hhat gene function. These mice may be useful for studying craniofacial development.

Donating Investigator

Trevor Williams, University of Colorado, Denver

Genetic overview

Genetic Background	Generation

Hhat^{Tg(TFAP2A-cre)1Will}

Allele Type
Transgenic (Recombinase-expressing, Null/Knockout)

View Genetics

Research Applications

Developmental Biology Research
Neurobiology Research
Research Tools

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These Creface transgenic mice express Cre recombinase under the control of the human transcription factor AP-2, alpha (Tfap2a) promoter/enhancer elements. A polyadenylation sequence followed by parts of exons 5-6 of Tfap2a, encoding the frontonasal prominence (FNP) and limb enhancer elements, was inserted downstream of the cre sequence. AP-2alpha is a transcription factor expressed in the neural tube, and in cranial and cardiac neural crest cells in the developing embryo, as well as in the progress zone of the limb bud, the developing kidney, the eye, and surface ectoderm. The transgene was found to have integrated into intron 9 of the hedgehog acyltransferase (Hhat) gene, abolishing Hhat gene function. HHAT deficiency has been associated with holoprosencephaly, failure of the forebrain to bifurcate, together with acrania and agnathia. Hemizygous mice are viable and fertile, while homozygotes are embryonic lethal. These mutants lack Hhat activity resulting in craniofacial development defects evident between E14.5 and E17.5. Homozygous embryos exhibit abnormal morphology of the frontonasal, mandibular, and maxillary processes. They also exhibit defects in the development of the cranium, eye, nasal cavity and septum, mouth, and palates. Neural crest morphology is also altered, as is midbrain and forebrain morphology. Expression of cre recombinase was detected in the embryonic face and limb mesenchyme. When crossed with a strain containing a loxP site-flanked sequence, Cre-mediated recombination results in deletion of the flanked sequence in cre-expressing cells.

For example, when bred to STOCK Tfap2a^tm2Will/J mice (Stock No. 023406) expressing a floxed-Tfap2a gene, frontonasal knockout (FKO) mice exhibit midfacial growth anomalies including shortened snouts and wide-set eyes by postnatal day 15.

Development

The Creface transgene was designed with a cre-recombinase sequence driven by the human transcription factor AP-2, alpha (Tfap2a) promoter/enhancer elements. A polyadenylation sequence followed by parts of exons 5-6 of Tfap2a, encoding the frontonasal prominence (FNP) and limb enhancer elements, was inserted downstream of the cre sequence. The transgene was microinjected into fertilized FVB oocytes and founder mice were bred to FVB mice (See SNP note below). This transgene integrated into intron 9 of the hedgehog acyltransferase (Hhat) gene. Upon arrival at The Jackson Laboratory, transgenic mice were bred to FVB/NJ inbred mice (Stock No. 001800) to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Six of the 27 markers throughout the genome were segregating from an unknown source.

Expression Data

Expressed Gene	cre, cre recombinase, bacteriophage P1
Site of Expression	Expression of cre recombinase was detected in the embryonic face and limb mesenchyme.

Control Suggestions

Wild-type from the colony

Approximate Controls

001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Selected References

Nelson DK; Williams T. 2004. Frontonasal process-specific disruption of AP-2alpha results in postnatal midfacial hypoplasia, vascular anomalies, and nasal cavity defects. Dev Biol 267(1):72-92PubMed: 14975718 MGI: J:88829

View All References

Genetics

Hhat^{Tg(TFAP2A-cre)1Will}

Allele Symbol: Hhat^{Tg(TFAP2A-cre)1Will}

Allele Name	transgene insertion 1, Trevor Williams
Allele Type	Transgenic (Recombinase-expressing, Null/Knockout)
Allele Synonym(s)	Hhat^{Tg(TFAP2A-cre)1Will}; transgene insertion 1, Trevor Williams
Gene Symbol and Name	Hhat, hedgehog acyltransferase
Gene Synonym(s)	AP-2CRE; Skn; RGD1311746; Tg(TFAP2A-cre)1Will; AI462858; 2810432O22Rik; SKI1; RIKEN cDNA 2810432O22 gene; transgene insertion 1, Trevor Williams; expressed sequence AI462858; MART2; 2810432O22Rik; Tg(TFAP2A-cre)1Will
Promoter	TFAP2A, transcription factor AP-2 alpha, human
Expressed Gene	cre, cre recombinase, bacteriophage P1
Site of Expression	Expression of cre recombinase was detected in the embryonic face and limb mesenchyme.
Strain of Origin	Not Specified
Chromosome	1
Molecular Note	This transgenic construct consisted of 200 bp of human TFAP2A (TCFAP2A) promoter sequence (encoding a specific enhancer element) followed by NLS-cre, an SV40 polyA signal, and a 1.8 kb TFAP2A genomic fragment extending from within exon 5 through a portion of exon 6. The human intron 5 sequence includes the frontonasal prominence- and limb-specific enhancer. Expression of cre recombinase was detected in the embryonic face and limb mesenchyme. New research has determined that the transgene inserted into intron 9 of the Hhat locus. This insertion creates a non-functional allele.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

chondrodysplasia-pseudohermaphroditism syndrome

Research Areas By Genotype

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

Developmental Biology Research
- Craniofacial and Palate Defects
  - Orofacial clefting-specific cre expression
- Embryonic Lethality (Homozygous)
Neurobiology Research
- Cre-lox System
  - Cre Recombinase expression in neural tissue
Research Tools
- Cre-lox System
  - Cre Recombinase Expression
  - Cre Recombinase Expression: Germline/Embryonic Expression

Mammalian Phenotype Terms by Genotype

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

Genotype: Hhat^{Tg(TFAP2A-cre)1Will}/Hhat^{Tg(TFAP2A-cre)1Will}
Not Specified

cardiovascular system phenotype

hemorrhage
- large areas of pooling blood are observed in anterior region of embryo

craniofacial phenotype

abnormal cranium morphology
- skeletal elements of cranium are reduced in size in association with diminished zone of proliferating chondrocytes

abnormal mandible morphology
- dentary bones lack condyle, angular and coronoid processes at E17.5

abnormal mandibular prominence morphology
- hypoplastic at E9.5-10.5 resulting in narrow protruding midface by E14.5 with more pronounced mandibular hypoplasia

abnormal maxillary prominence morphology
- hypoplastic at E9.5-10.5 resulting in narrow protruding midface by E14.5 with more pronounced maxillary hypoplasia

abnormal nasal capsule morphology
- nasal cartilage is absent or hypoplastic at E15.5

abnormal nasal cavity morphology
- E14.5 embryos possess a single discontinuous nasal cavity

abnormal oral cavity morphology
- oral cavity is considerably narrower than in controls at E14.5

abnormal palatal shelf elevation
- embryos display defects in the vertical extension of palatal shelves

abnormal palatal shelf fusion at midline
- embryos display defects in the medial growth of palatal shelves toward the midline

abnormal palate development
- at E14.5 palatal shelves are not easily identifiable

absent interparietal bone
- observed at E17.5

absent mandibular angle

absent mandibular condyloid process

absent mandibular coronoid process

absent nasal septum
- missing in E14.5 embryos

absent parietal bone
- observed at E17.5

absent supraoccipital bone
- observed at E17.5

absent tooth placode
- incisor and alveolar molar tooth primordia are missing at E17.5

acrania
- observed at E17.5

agnathia
- at E17.5 only rudimentary premaxilla, maxilla and dentary bones are observed

arrest of tooth development
- tooth development is disrupted

small basioccipital bone
- reduced in size and misshapen at E17.5

small exoccipital bone
- reduced in size and misshapen at E17.5

small frontonasal prominence
- frontonasal region is reduced in size by E10.5 so that only a single slit is present

tongue hypoplasia
- observed at E14.5

digestive/alimentary phenotype

abnormal palatal shelf elevation
- embryos display defects in the vertical extension of palatal shelves

abnormal palatal shelf fusion at midline
- embryos display defects in the medial growth of palatal shelves toward the midline

abnormal palate development
- at E14.5 palatal shelves are not easily identifiable

tongue hypoplasia
- observed at E14.5

embryo phenotype

abnormal neural crest cell morphology

abnormal neural crest morphology
- neural crest derived frontonasal, maxillary, mandibular and prospective palatal mesenchyme displays considerably more apoptosis than controls
- neural crest lineages are altered compared to wild type

decreased embryo size
- embryos as smaller than controls at E10.5

endocrine/exocrine gland phenotype

abnormal fetal Leydig cell differentiation
- marker analysis indicates that differentiation of fetal Leydig cells and steroidogenesis are not initiated at E12.5 and E13.5

abnormal testis cord formation
- alteration of the size and shape of testis cords which appear irregular and anastomotic
- decrease in testis cord numbers
- Normal - however, differentiation of Sertoli cells appears normal

abnormal testis development
- Normal - however, female germ cells are normal in numbers and ovarian differentiation occurs normally
- testis development is severely affected by E12.5
- the interstitial compartment of the developing testes at E13.5 and E15.5 exhibits a high cellular density typical of irregular and dense connective tissues

abnormal testis morphology
- testicular dysgenesis

small testis
- drastic reduction in testis size that is apparent from E12.5 to E15.5

growth/size/body region phenotype

abnormal nasal capsule morphology
- nasal cartilage is absent or hypoplastic at E15.5

abnormal nasal cavity morphology
- E14.5 embryos possess a single discontinuous nasal cavity

abnormal oral cavity morphology
- oral cavity is considerably narrower than in controls at E14.5

abnormal palatal shelf elevation
- embryos display defects in the vertical extension of palatal shelves

abnormal palatal shelf fusion at midline
- embryos display defects in the medial growth of palatal shelves toward the midline

abnormal palate development
- at E14.5 palatal shelves are not easily identifiable

absent nasal septum
- missing in E14.5 embryos

absent tooth placode
- incisor and alveolar molar tooth primordia are missing at E17.5

arrest of tooth development
- tooth development is disrupted

decreased embryo size
- embryos as smaller than controls at E10.5

tongue hypoplasia
- observed at E14.5

homeostasis/metabolism phenotype

edema
- outer layer of skin is displaced from body cavity

limbs/digits/tail phenotype

oligodactyly
- observed at E14.5

mortality/aging

prenatal lethality, complete penetrance
- no viable animals are recovered postnatally

nervous system phenotype

abnormal forebrain morphology

abnormal midbrain morphology

abnormal neural crest cell morphology

abnormal neural crest morphology
- neural crest derived frontonasal, maxillary, mandibular and prospective palatal mesenchyme displays considerably more apoptosis than controls
- neural crest lineages are altered compared to wild type

diencephalon hypoplasia
- diencephalic hypoplasia is observed by E9.5 with agenesis of prosomere 2

small embryonic telencephalon
- smaller telencephalic vesicles are observed by E9.5

reproductive system phenotype

abnormal fetal Leydig cell differentiation
- marker analysis indicates that differentiation of fetal Leydig cells and steroidogenesis are not initiated at E12.5 and E13.5

abnormal testis cord formation
- alteration of the size and shape of testis cords which appear irregular and anastomotic
- decrease in testis cord numbers
- Normal - however, differentiation of Sertoli cells appears normal

abnormal testis development
- Normal - however, female germ cells are normal in numbers and ovarian differentiation occurs normally
- testis development is severely affected by E12.5
- the interstitial compartment of the developing testes at E13.5 and E15.5 exhibits a high cellular density typical of irregular and dense connective tissues

abnormal testis morphology
- testicular dysgenesis

small testis
- drastic reduction in testis size that is apparent from E12.5 to E15.5

respiratory system phenotype

abnormal nasal capsule morphology
- nasal cartilage is absent or hypoplastic at E15.5

abnormal nasal cavity morphology
- E14.5 embryos possess a single discontinuous nasal cavity

absent nasal septum
- missing in E14.5 embryos

skeleton phenotype

abnormal cartilage development
- diminished chondrogenesis of calvarial, nasal and otic mesenchyme is observed with cranial cartilage elements hypoplastic or missing at E15.5

abnormal cranium morphology
- skeletal elements of cranium are reduced in size in association with diminished zone of proliferating chondrocytes

abnormal mandible morphology
- dentary bones lack condyle, angular and coronoid processes at E17.5

abnormal nasal capsule morphology
- nasal cartilage is absent or hypoplastic at E15.5

abnormal vertebral column morphology
- staining for cartilage in the vertebral column is absent at E15.5

absent interparietal bone
- observed at E17.5

absent mandibular angle

absent mandibular condyloid process

absent mandibular coronoid process

absent parietal bone
- observed at E17.5

absent supraoccipital bone
- observed at E17.5

absent tooth placode
- incisor and alveolar molar tooth primordia are missing at E17.5

acrania
- observed at E17.5

agnathia
- at E17.5 only rudimentary premaxilla, maxilla and dentary bones are observed

arrest of tooth development
- tooth development is disrupted

failure of bone ossification
- ossified bone is completely absent in skull and jaw at E15.5

small basioccipital bone
- reduced in size and misshapen at E17.5

small exoccipital bone
- reduced in size and misshapen at E17.5

vision/eye phenotype

abnormal eye development
- in some embryos eye remains embedded in brain tissue; this lack of surface ectoderm contact results in failure to form tissues such as the cornea

abnormal optic vesicle formation

absent cornea
- failure to form the cornea

microphthalmia

References

Nelson DK; Williams T. 2004. Frontonasal process-specific disruption of AP-2alpha results in postnatal midfacial hypoplasia, vascular anomalies, and nasal cavity defects. Dev Biol 267(1):72-92PubMed: 14975718 MGI: J:88829

Additional - Hhat^{Tg(TFAP2A-cre)1Will} related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Hhat^{Tg(TFAP2A-cre)1Will}
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wildtype (non-carrier) mice from the colony. Homozygous mice are embryonic lethal.
- Additional Breeding and Husbandry Support
Citation
When using the AP-2CRE mouse strain in a publication, please cite the originating article(s) and include JAX stock #023407 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
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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Hhat<Tg(TFAP2A-cre)1Will>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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Also Known As: AP-2CRE, CrefaceT

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

HhatTg(TFAP2A-cre)1Will

Allele Symbol: HhatTg(TFAP2A-cre)1Will

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: HhatTg(TFAP2A-cre)1Will/HhatTg(TFAP2A-cre)1WillNot Specified

cardiovascular system phenotype

craniofacial phenotype

digestive/alimentary phenotype

embryo phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

limbs/digits/tail phenotype

mortality/aging

nervous system phenotype

reproductive system phenotype

respiratory system phenotype

skeleton phenotype

vision/eye phenotype

References

Additional - HhatTg(TFAP2A-cre)1Will related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As: AP-2CRE, Creface^T

Hhat^{Tg(TFAP2A-cre)1Will}

Allele Symbol: Hhat^{Tg(TFAP2A-cre)1Will}

Genotype: Hhat^{Tg(TFAP2A-cre)1Will}/Hhat^{Tg(TFAP2A-cre)1Will}
Not Specified

Additional - Hhat^{Tg(TFAP2A-cre)1Will} related