These CREBIR mice express a transgene containing an inducible and reversible cAMP responsive element binding protein 1 (CREB1) repressor.
Alcino J. Silva, University of California, Los Angeles
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inserted expressed sequence) |
These transgenic mice have a tamoxifen inducible cAMP responsive element binding protein 1 (Creb1) repressor driven by the mouse calcium/calmodulin-dependent protein kinase II alpha promoter. The transgene insert contains a fusion product involving a mutant Creb1 isoform (CREBS133A) and a mutant form of the human estrogen receptor ligand binding domain (LBDG521R). Expression of the transgene is detected in the hippocampus and cortex as analyzed by Northern and Western blot. In addition, transgene expression is detected in the amygdala by RT-PCR analysis. The mutant human estrogen receptor does not bind natural ligand at physiological concentrations but will bind the synthetic ligand, 4-hydroxytamoxifen. Tamoxifen administration activates the repressor, reducing cyclic AMP responsive element-mediated transcription. When the repressor system is activated, mutant mice exhibit impaired long term memory consolidation and retrieval in fear conditioning training. The Donating Investigator did not attempt to make the strain homozygous, and does not believe homozygotes would be viable. Publication observations were made on B6C3F1 animals. This mutant mouse strain may be useful in studies of the molecular basis for memory and learning.
A transgenic construct containing sequence encoding the CREBIR( cAMP responsive element binding protein 1 repressor/estrogen ligand-binding domain) fusion gene under the control of the mouse calcium/calmodulin-dependent protein kinase II alpha promoter and a polyadenylation site was introduced into C3H donor eggs.
Expressed Gene | ESR1, estrogen receptor 1, human |
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Site of Expression |
Allele Name | transgene insertion 3, Alcino Silva |
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Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | CREBIR; CREB-IR; line C |
Gene Symbol and Name | Tg(Camk2a-Creb1/ESR1)3Sva, transgene insertion 3, Alcino Silva |
Gene Synonym(s) | |
Promoter | Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory |
Expressed Gene | ESR1, estrogen receptor 1, human |
Strain of Origin | C3H/HeNTac |
Chromosome | UN |
General Note | In transgenic mice tamoxifen administration causes a reduction in cyclic AMP responsive element-mediated transcription These mice tehn exhibit impaired long term memory consolidation and retrieval in fear conditioning training. |
Molecular Note | The transgene expresses a fusion protein comprising the tamoxifen-, but not estrogen-inducible G521R mutant of the human estrogen receptor ligand binding domain joined to the transcriptionally inactive S133A mutant of cAMP responsive element binding protein 1 (CREB1), which competitively inhibits binding of native CREB1 to cAMP response elements, under control of the promoter of mouse calcium/calmodulin-dependent protein kinase II alpha, which in the adult animal directs expression to the excitatory neurons of forebrain regions including the hippocampus, amygdala, cortex and striatum. Transcription of the fusion gene in cortex, hippocampus and striatum of transgenic mice was confirmed by reverse transcription followed by polymerase chain reaction (RT-PCR). RT-PCR analysis detected transgene expression in the amygdala. Northern and Western blot analyses detected expression of the transgene in the hippocampus and cortex. |
Mutations Made By | Rachel Chen, University of California, Los Angeles |
The resulting male transgenic mice were backcrossed for 5 generations on the C3H background. The strain is maintained as a hemizygote.
When using the CREBIR mouse strain in a publication, please cite the originating article(s) and include JAX stock #004995 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Hemizygous or Non carrier for Tg(Camk2a-Creb1/ESR1)3Sva |
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