Overview

Also Known As:Wnt-1/GAL4/cre-11

These Wnt-1/GAL4/cre-11 transgenic mice have expression of both Cre recombinase and the GAL4 transcriptional activator directed to midbrain and developing neural tube by the wingless-related MMTV integration site 1 (Wnt1) promoter/regulatory sequences. When Wnt-1/GAL4/cre-11 transgenic mice are bred to mice containing loxP site-flanked sequences, cre-mediated recombination results in deletion of the floxed sequences in the midbrain and developing neural tube of the resulting offspring.

Wnt-1/GAL4/cre-11 mice exhibit transgenic overexpression of Wnt1, both within and outside of the expected pattern of expression, which results in increased activation of WNT signaling, along with midbrain enlargement and accompanying loss of midbrain dopaminergic neurons (Lewis et al. 2013 Dev Biol 379:229). Further, it was reported in Goodwin et al. 2019 Genome Res. 29:494, that the Wnt1-cre transgene integrated into chromosome 11 causing a 31,283 bp deletion in the H2afv locus. In Stock No. 009107, founder line 1 had a copy number of greater than 5.

Donating Investigator

David H. Rowitch, University of California, San Francisco

Genetic overview

Genetic Background	Generation

Tg(Wnt1-GAL4)11Rth

Allele Type
Transgenic (Inserted expressed sequence)

H2az2^{Tg(Wnt1-cre)11Rth}

Allele Type
Transgenic (Recombinase-expressing)

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Research Applications

Research Tools
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

When homozygous for both co-injected transgenes, Wnt-1/GAL4/cre-11 transgenic mice are viable and fertile. Both Cre recombinase and the GAL4 transcriptional activator are expressed under the direction of wingless-related MMTV integration site 1 (Wnt1) promoter/regulatory sequences. Cre recombinase activity is detected in the Wnt1 pattern of expression: in the midbrain by 8.5 dpc and, after neural tube closure, in the dorsal and ventral midlines of the midbrain and caudal diencephalon, midbrain-hindbrain junction and dorsal spinal cord. Double transgenic mice exhibit psychiatric disorder-related behavioral abnormalities. Males, specifically, exhibit increased locomotor activity, increased anxiety, and decreased social interaction, while females exhibit impaired short-term spatial memory and nesting behavior. Both sexes have disordered cholinergic and glutamatergic fiber tracts from the medial habenula neurons in the interpeduncular nucleus.

Wnt-1/GAL4/cre-11 mice exhibit transgenic overexpression of Wnt1, both within and outside of the expected pattern of expression, which results in increased activation of WNT signaling, along with midbrain enlargement and accompanying loss of midbrain dopaminergic neurons (Lewis et al. 2013 Dev Biol 379:229).

When Wnt-1/GAL4/cre-11 transgenic mice are bred to mice containing loxP site-flanked sequences, cre-mediated recombination results in deletion of the floxed sequences in the midbrain and developing neural tube of the resulting offspring.

Development

The transgenic line Wnt-1/GAL4/cre-11 was created by Dr. David H. Rowitch and Andrew P. McMahon (Harvard University). These mice resulted from co-injection of both the pWEXP2-GAL4 transgene (Wnt1-GAL4) and the pWEXP3C-cre transgene (Wnt1-Cre) into pronuclei of B6CBAF1/J (C57BL/6JxCBA/J) zygotes. Double transgenic mice from founder line 11 were obtained and bred with Swiss albino outbred mice. Double transgenic albino mice were sent to The Jackson Laboratory Repository in 2000 (as Stock No. 003829). Upon arrival, mice were bred together to establish the colony. The description of each transgene is below.

The pWEXP2-GAL4 transgene (Wnt1-GAL4) was designed by Dr. David H. Rowitch and Andrew P. McMahon (Harvard University) with the mouse Wnt1 promoter/enhancer elements upstream of a sequence encoding the full-length yeast GAL4 gene. Specifically, the Wnt1-GAL4 transgene was created by inserting a sequence encoding the full-length yeast GAL4 gene into a 10 kbp modified mouse Wnt1 genomic sequence at a polylinker site between the promoter and enhancer (the Wnt1 genomic sequence spans from approximately 1 kbp upstream of the translation initiation codon to approximately 5.5 kbp downstream of the polyA signal, and is modified with a polylinker that disrupts the translational start site and a reverse-oriented neo cassette in 3' UTR of exon 4).

The pWEXP3C-cre transgene (Wnt1-Cre) was designed by Dr. David H. Rowitch and Andrew P. McMahon (Harvard University) with the mouse Wnt1 promoter/enhancer elements upstream of a Cre recombinase cDNA sequence. Specifically, the Wnt1-Cre transgene was created by inserting the Cre recombinase cDNA into a 10 kbp modified mouse Wnt1 genomic sequence at a polylinker site between the promoter and enhancer (the Wnt1 genomic sequence spans from approximately 1 kbp upstream of the translation initiation codon to approximately 5.5 kbp downstream of the polyA signal, and is modified with a polylinker that disrupts the translational start site and a reverse-oriented neo cassette in 3' UTR of exon 4).
In Goodwin et al. 2019 Genome Res. 29:494, it was discovered that the Wnt1-cre transgene integrated into chromosome 11 causing a 31,283 bp deletion in the H2afv locus. In Stock No. 009107, founder line 1 had a copy number of greater than 5.

Expression Data

Expressed Gene	GAL4, transcriptional activator GAL4, yeast
Site of Expression	embryonic neural tube, midbrain, dorsal and ventral midlines of the midbrain and caudal diencephalon, the mid-hindbrain junction and dorsal spinal cord
Expressed Gene	cre, cre recombinase, bacteriophage P1
Site of Expression	embryonic neural tube, midbrain, dorsal and ventral midlines of the midbrain and caudal diencephalon, the mid-hindbrain junction and dorsal spinal cord

Control Suggestions

Noncarrier

Additional Information

Considerations for Choosing Controls

Selected References

Danielian PS; Muccino D; Rowitch DH; Michael SK; McMahon AP. 1998. Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr Biol 8(24):1323-6PubMed: 9843687 MGI: J:69326

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Genetics

Tg(Wnt1-GAL4)11Rth

Allele Symbol: Tg(Wnt1-GAL4)11Rth

Allele Name	transgene insertion 11, David H Rowitch
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	Tg(Wnt1-GAL4)11Rth; transgene insertion 11, David H Rowitch
Gene Symbol and Name	Tg(Wnt1-GAL4)11Rth, transgene insertion 11, David H Rowitch
Gene Synonym(s)	Wnt-1/GAL4; WEXP-GAL4
Promoter	Wnt1, wingless-type MMTV integration site family, member 1, mouse, laboratory
Expressed Gene	GAL4, transcriptional activator GAL4, yeast
Site of Expression	embryonic neural tube, midbrain, dorsal and ventral midlines of the midbrain and caudal diencephalon, the mid-hindbrain junction and dorsal spinal cord
Strain of Origin	(C57BL/6J x CBA/J)F1
Chromosome	UN
General Note	Six lines were generated. Homozygous transgenic mice that are also homozygous for Tg(Wnt1-cre)11Rth are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Both Cre recombinase and the GAL4 transcriptional activator are expressed under the direction of Wnt1 regulatory sequences. Regulated expression initially occurs in the midbrain. After neural tube closure, expression occurs in the dorsal and ventral midlines of the midbrain and caudal diencephalon, the midbrain-hindbrain junction, and in the dorsal spinal cord.
Molecular Note	The transgene contains the yeast GAL4 gene directed by Wnt1 promoter/enhancer sequences. Expression of the transgene matches that of the endogenous Wnt1.
Mutations Made By	David Rowitch, University of California, San Francisco

H2az2^{Tg(Wnt1-cre)11Rth}

Allele Symbol: H2az2^{Tg(Wnt1-cre)11Rth}

Allele Name	transgene insertion 11, David H Rowitch
Allele Type	Transgenic (Recombinase-expressing)
Allele Synonym(s)	transgene insertion 11, David H Rowitch; H2az2^{Tg(Wnt1-cre)11Rth}
Gene Symbol and Name	H2az2, H2A.Z histone variant 2
Gene Synonym(s)	H2A.Z-2; H2AV; RIKEN cDNA C530002L11 gene; C530002L11Rik; C530002L11Rik; H2A.Z2; H2AFV
Promoter	Wnt1, wingless-type MMTV integration site family, member 1, mouse, laboratory
Expressed Gene	cre, cre recombinase, bacteriophage P1
Site of Expression	embryonic neural tube, midbrain, dorsal and ventral midlines of the midbrain and caudal diencephalon, the mid-hindbrain junction and dorsal spinal cord
Strain of Origin	(C57BL/6J x CBA/J)F1/J
Chromosome	11
General Note	Homozygous transgenic mice that are also homozygous for Tg(Wnt1-GAL4)11Rth are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities.
Molecular Note	The Wnt1 promoter preceded the cre recombinase coding sequence which was followed downstream by the Wnt1 enhancer. The Wnt1 regulatory sequences initially direct expression in the midbrain. After neural tube closure, expression occurs in the dorsal and ventral midlines of the midbrain and caudal diencephalon, the midbrain-hindbrain junction and in the dorsal spinal cord. Line 11 inserted into the gene at 6425500-6456783 (Build GRCm38/mm10) resulting in a 31,283 bp deletion. Founder line x has a copy number of greater than 5.
Mutations Made By	David Rowitch, University of California, San Francisco

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Cre-lox System
  - Cre Recombinase Expression
- GAL4-UAS System
  - GAL4 transcriptional activator
Developmental Biology Research
- Craniofacial and Palate Defects
  - Orofacial clefting-specific cre expression

Mammalian Phenotype Terms by Genotype

References

Danielian PS; Muccino D; Rowitch DH; Michael SK; McMahon AP. 1998. Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr Biol 8(24):1323-6PubMed: 9843687 MGI: J:69326

Additional References

Pietri T; Eder O; Blanche M; Thiery JP; Dufour S. 2003. The human tissue plasminogen activator-Cre mouse: a new tool for targeting specifically neural crest cells and their derivatives in vivo. Dev Biol 259(1):176-87PubMed: 12812797 MGI: J:92369

Additional - H2az2^{Tg(Wnt1-cre)11Rth} related

Additional - Tg(Wnt1-GAL4)11Rth related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Generic Cre Melt Curve Analysis
- Standard PCR:Tg(Wnt1-GAL4)11Rth-Chr11
- Genotyping resources and troubleshooting
Breeding Considerations

This strain has two co-injected transgenes that segregate together. When maintaining a live colony, transgenic carrier mice (harboring both co-injected transgenes) may be bred together, to to wildtype (noncarrier) mice from the colony, or occasionally to B6CBAF1/J hybrid mice (Stock No. 100011). Strain aggression is common and may require individual housing. On a different genetic background (see Stock No. 009107), it is reported that homozygous mice may be lethal as some offspring from transgenic carrier parents die around two months of age.
- Additional Breeding and Husbandry Support
Citation
When using the Wnt-1/GAL4/cre-11 mouse strain in a publication, please cite the originating article(s) and include JAX stock #003829 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
	Hemizygous or Non carrier for Tg(Wnt1-cre)11Rth, Hemizygous or Non carrier for Tg(Wnt1-GAL4)11Rth

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Also Known As:Wnt-1/GAL4/cre-11

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(Wnt1-GAL4)11Rth

Allele Symbol: Tg(Wnt1-GAL4)11Rth

H2az2Tg(Wnt1-cre)11Rth

Allele Symbol: H2az2Tg(Wnt1-cre)11Rth

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional References

Additional - H2az2Tg(Wnt1-cre)11Rth related

Additional - Tg(Wnt1-GAL4)11Rth 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

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

H2az2^{Tg(Wnt1-cre)11Rth}

Allele Symbol: H2az2^{Tg(Wnt1-cre)11Rth}

Additional - H2az2^{Tg(Wnt1-cre)11Rth} related