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Strain Name:

B6.Cg-Tg(Camk2a-Crebbp*)1364Tabe/J

Stock Number:

007574

Availability:

Repository- Live

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General Terms and Conditions

Former Name      B6(SJL)-Tg(Camk2a-Crebbp*)1364Tabe/J    (Changed: 29-JUN-07 )
Genes & Alleles   Camk2a;   Crebbp;   Tg(Camk2a-Crebbp*)1364Tabe;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Transgenic
Mating SystemNoncarrier x Hemizygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Ted Abel,   University of Pennsylvania
GenerationN10+ (20-MAR-08)

Strain Description
Mice hemizygous for this "CaMKIIa-FLAG-CBPD1" transgene are viable and fertile. Expression of this FLAG-epitope tagged, dominant negative truncation of the CREB-binding protein (FLAG-CBPD1) is spatially directed to neurons in the forebrain (hippocampus, amygdala, striatum, and cortex) and temporally directed to postnatal development by the CaMKIIa promoter. This dominant negative mutant form of CBP (designed to interrupt transcription factors utilizing CBP as a coactivator for the expression of their target genes) is expressed from the transgene at 95% of endogenous CBP levels in the hippocampus and 84% of endogenous CBP levels in the cortex. Hemizygous mice exhibit hippocampus-dependent memory deficits (such as reduced long-term potentiation, defective spatial learning, and impaired contextual fear conditioning) with none of the developmental impairments observed in CBP-deficient mutant models. These CaMKIIa-FLAG-CBPD1 transgenic mice may be useful for behavioral and learning neuroscience research including hippocampal synaptic plasticity, spatial/contextual hippocampus-dependent memory, and cognitive endophenotypes of Rubinstein-Taybi Syndrome (RTS).

Strain Development
A transgenic construct was designed with a FLAG-epitope sequence tag at the amino terminus of a truncated mouse CREB-binding protein sequence (called CBPD1; lacking the coding sequence for amino acids 1084-2441), all flanked by an artificial intron and splice sites at the 5' end and by a polyadenylation signal from SV40 at the 3' end. This FLAG-CBPD1 sequence was then placed downstream of 8.5 kb of the mouse CaMKIIa promoter. The resulting 13 kb "CaMKIIa-FLAG-CBPD1" transgene was microinjected into the pronuclei of B6SJLF1 zygotes. Founder line 1364 (with 25-30 copies of the transgene) was established and backcrossed to C57BL/6J inbred mice for at least 9 generations prior to arrival at The Jackson Laboratory.

Mammalian Phenotype Terms assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Tg(Camk2a-Crebbp*)1364Tabe/0

        involves: C57BL/6 * SJL
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype (MGI Ref ID J:121812)
    • mutants show normal short-term memory and cued fear conditioning relative to control littermates
    • abnormal contextual conditioning (MGI Ref ID J:121812)
      • in foot shock paradigm, upon re-exposure to conditioned context 24 hours after training, mutants show decreased freezing compared to wild-type littermates
    • abnormal spatial learning (MGI Ref ID J:121812)
      • mice show deficit in spatial learning, with significant impairment in acquisition of Morris water maze hidden platform task; mean escape latency is lower in wild-type mice, whereas transgenic mice reach a plateau on fifth day of training; wild-type mice show a preference for the target quadrant relative to transgenic mice
    • increased thigmotaxis (MGI Ref ID J:121812)
      • mutants display increased thigmotaxis (swimming in outer 10% of pool) during training compared to littermate controls
  • nervous system phenotype
  • reduced long term potentiation (MGI Ref ID J:121812)
    • in hippocampal slices treated with the D1 dopaminergic agonist chloro-APB followed by a single 1 second, 100 Hz train stimulus, average potentiation is significantly at 60 minutes relative to wild-type

Gene & Allele Details

Allele Symbol Tg(Camk2a-Crebbp*)1364Tabe
Allele Name transgene insertion 1364, Ted Abel
Common Name(s) CaMKIIalpha-CBPdelta1; CaMKIIalpha-FLAG-CBPdelta1; Tg(Camk2a-Crebbp)1364Tabe;
Mutation Made By Ted Abel,   University of Pennsylvania
Strain of Origin(C57BL/6 x SJL)F1
Expressed Gene Crebbp, CREB binding protein, mouse, laboratory
Promoter Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory
Molecular Note A transgenic construct was designed with a FLAG-epitope sequence tag at the amino terminus of a truncated mouse CREB-binding protein sequence (called CBPdelta1; lacking the coding sequence for amino acids 1084-2441), all flanked by an artificial intron and splice sites at the 5' end and by a polyadenylation signal from SV40 at the 3' end. This FLAG-CBPD1 sequence was then placed downstream of 8.5 kb of the mouse CaMKIIalpha promoter. The resulting 13 kb "CaMKIIalpha-FLAG-CBPdelta1" transgene was microinjected into the pronuclei of B6SJLF1 zygotes. Expression of the truncated product is restricted to the post-natal hippocampus, striatum, amygdala, and cortex. [MGI Ref ID J:121812]

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Tg(Camk2a-Crebbp*)1364Tabe

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygous mice can be bred together or to wildtype siblings or C57BL/6J inbred mice.

Related Strains

View Strains carrying other alleles of Camk2a     (10 strains)

Strains carrying other alleles of Crebbp
004069   B6.129S6-Crebbptm1Dli/J
View Strains carrying other alleles of Crebbp     (1 strain)

Additional Web Information

Congenic Nomenclature

Animal Health Reports

Room Number           AX11

Research Applications

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

Cell Biology Research
Transcriptional Regulation

Neurobiology Research
Behavioral and Learning Defects

References

Selected Reference(s)

Wood MA; Kaplan MP; Park A; Blanchard EJ; Oliveira AM; Lombardi TL; Abel T. 2005. Transgenic mice expressing a truncated form of CREB-binding protein (CBP) exhibit deficits in hippocampal synaptic plasticity and memory storage. Learn Mem 12(2):111-9. [PubMed: 15805310]  [MGI Ref ID J:121812]

Price and Supply Information

Strain Name: B6.Cg-Tg(Camk2a-Crebbp*)1364Tabe/J
Stock Number: 007574

Price Details

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

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The Jackson Laboratory's Genotype Promise

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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