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.
Trevor Williams, University of Colorado, Denver
Genetic Background | Generation |
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Allele Type |
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Transgenic (Recombinase-expressing, Null/Knockout) |
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 Tfap2atm2Will/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.
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.
Expressed Gene | cre, cre recombinase, bacteriophage P1 |
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Site of Expression | Expression of cre recombinase was detected in the embryonic face and limb mesenchyme. |
Allele Name | transgene insertion 1, Trevor Williams |
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Allele Type | Transgenic (Recombinase-expressing, Null/Knockout) |
Allele Synonym(s) | AP-2CRE; Ap2-Cre; CrefaceT; Tg(TFAP2A-cre)1Will |
Gene Symbol and Name | Hhat, hedgehog acyltransferase |
Gene Synonym(s) | |
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. |
When maintaining a live colony, heterozygous mice may be bred to wildtype (non-carrier) mice from the colony. Homozygous mice are embryonic lethal.
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Hhat<Tg(TFAP2A-cre)1Will> |
Frozen Mouse Embryo | STOCK Hhat<Tg(TFAP2A-cre)1Will>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Hhat<Tg(TFAP2A-cre)1Will>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Hhat<Tg(TFAP2A-cre)1Will>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | STOCK Hhat<Tg(TFAP2A-cre)1Will>/J Frozen Embryo | $3373.50 |
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