C3H-Tg(Camk2a-Creb1/ESR1)3Sva/J

Stock number: 004995
Product name: CREB^IR
Research areas: Neurobiology Research

Description

These CREB^IR mice express a transgene containing an inducible and reversible cAMP responsive element binding protein 1 (CREB1) repressor.

Detailed description

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 (CREB^S133A) and a mutant form of the human estrogen receptor ligand binding domain (LBD^G521R). 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.

Development

A transgenic construct containing sequence encoding the CREB^IR( 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.

Allele

Symbol: Tg(Camk2a-Creb1/ESR1)3Sva
Name: transgene insertion 3, Alcino Silva
MGI accession ID: MGI:3051752
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Camk2a-Creb1/ESR1)3Sva
Marker name: transgene insertion 3, Alcino Silva
Chromosome: UN
Strain of origin: C3H/HeNTac
Expressed genes: ESR1,estrogen receptor 1,human
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.
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.