Strain Name:

B6.129S2-Creb1tm1Gsc/J

Stock Number:

004445

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Availability:

Cryopreserved - Ready for recovery

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names CREB-    (Changed: 15-DEC-04 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Alcino J. Silva,   University of California, Los Angeles

Description
Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. In heterozygote crosses, the number of homozygous progeny born (15%) does not reach the expected Mendelian ratio indicating low survival of homozygous embryos. No gene product (mRNA or alpha and delta isoform proteins) is detected. The beta isoform gene product is up regulated. cAMP response element modulation protein expression is up regulated 2- to 3-fold. Although fear conditioning and Morris water maze testing demonstrate that homozygous mice have normal learning and short-term memory, long-term memory for cued and contextual conditioning is disrupted. Electrophysiological analysis of the hippocampus of mutant mice reveals abnormal long-term potentiation, which decays to baseline within 90 minutes, whereas wildtype controls display no decay. The long-term memory deficit exhibited by mutant mice can be overcome by additional spaced (10-60 minutes between trials) training. Homozygous mutant mice treated with chronic morphine administration exhibit reduced opiate tolerance and diminished morphine withdrawal. This mutant mouse strain may be useful in studies related to the molecular mechanisms of long-term memory and in studies related to the chronic effects of drug abuse.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 2. The construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Histiocytoma, Angiomatoid Fibrous   (CREB1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Creb1tm1Gsc/Creb1tm1Gsc

        involves: 129S2/SvPas
  • mortality/aging
  • decreased survivor rate
    • fewer than expected mice survive to adulthood (15% compared to an expected 25%)   (MGI Ref ID J:18749)
    • however, surviving mice exhibit normal histology and morphology   (MGI Ref ID J:18749)
  • postnatal lethality
    • fewer than expected mice survive to adulthood (15% compared to an expected 25%)   (MGI Ref ID J:18749)
    • however, surviving mice exhibit normal histology and morphology   (MGI Ref ID J:18749)
  • behavior/neurological phenotype
  • abnormal behavioral response to addictive substance
    • at high doses, mice develop a tolerance to morphine analgesia compared to wild-type mice   (MGI Ref ID J:34605)
    • decreased behavioral withdrawal response
      • following treatment with naloxone, mice chronically treated with morphine exhibit reduced withdrawal symptoms with no signs of sniffing or pstosis compared to similarly treated wild-type mice   (MGI Ref ID J:34605)
  • abnormal cued conditioning behavior
    • 2 and 24 hours after cued conditioning, all but 2 mice exhibit reduced freezing compared to wild-type mice   (MGI Ref ID J:20672)
    • mice receiving extra training still perform worse than wild-type mice   (MGI Ref ID J:20672)
    • however, cued conditioning after 30 and 60 minutes is normal   (MGI Ref ID J:20672)
  • abnormal spatial learning
    • while intensive training improves performance, mice perform worse than wild-type mice in a Morris water maze   (MGI Ref ID J:20672)
  • abnormal temporal memory
    • regardless of additional training, mice exhibit defects in long-term memory following contextual and cued conditioning compared to wild-type mice   (MGI Ref ID J:20672)
    • abnormal contextual conditioning behavior
      • 60 minutes and 24 hours after contextual conditioning, all but 1 mouse exhibit reduced freezing compared to wild-type mice   (MGI Ref ID J:20672)
      • mice receiving extra training still perform worse than wild-type mice   (MGI Ref ID J:20672)
      • however, contextual conditioning 30 minutes after conditioning is normal   (MGI Ref ID J:20672)
  • decreased vertical activity   (MGI Ref ID J:34605)
  • nervous system phenotype
  • abnormal CNS synaptic transmission
    • the ratio of field excitatory postsynaptic potential slope to fiber volley in untetanized hippocampal slices is increased 1.6-fold compared to in wild-type slices   (MGI Ref ID J:20672)
    • however, paired pulse facilitation is normal   (MGI Ref ID J:20672)
    • reduced long term potentiation
      • long term potentiation decays to baseline 90 minutes after tetanus unlike in wild-type mice that maintain stable LTP for 2 hours   (MGI Ref ID J:20672)
      • despite normal peak posttetanic potentiation, synaptic potentiation is lower than in wild-type mice as early as 10 minutes after titanic conditioning   (MGI Ref ID J:20672)
  • abnormal stellate ganglion morphology
    • stellate ganglion is larger than in controls at E17.5   (MGI Ref ID J:121244)
  • small superior cervical ganglion
    • SCG is smaller than in controls at E17.5   (MGI Ref ID J:121244)
View Research Applications

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

Creb1tm1Gsc related

Developmental Biology Research
Embryonic Lethality (Homozygous)
      incomplete

Neurobiology Research
Behavioral and Learning Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Creb1tm1Gsc
Allele Name targeted mutation 1, Gunther Schutz
Allele Type Targeted (Null/Knockout)
Common Name(s) CREB -; CREBalphadelta-; CREBalphadelta; CREBalphadelta;
Mutation Made By Maress Lacuesta,   University of California, Los Angeles
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Creb1, cAMP responsive element binding protein 1
Chromosome 1
Gene Common Name(s) 2310001E10Rik; 3526402H21Rik; AV083133; CREB; Creb; Creb-1; RIKEN cDNA 2310001E10 gene; RIKEN cDNA 3526402H21 gene; cyclic AMP responsive element binding protein; expressed sequence AV083133;
Molecular Note A promoterless neomycin resistance gene was inserted in frame into exon 2. RNase protection assays on RNA derived from liver of homozyogous mice demonstrated that no detectable alpha or delta isoform transcript was produced from this allele; however, a beta isoform transcript is upregulated (J:31886). Western blot analysis on liver extracts from homozygous mice confirmed that no alpha or delta isoform of the encoded protein was produced. [MGI Ref ID J:18749] [MGI Ref ID J:31886]

Genotyping

Genotyping Information

Genotyping Protocols

Creb1tm1Gsc, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Creb1tm1Gsc related

Balschun D; Wolfer DP; Gass P; Mantamadiotis T; Welzl H; Schutz G; Frey JU; Lipp HP. 2003. Does cAMP response element-binding protein have a pivotal role in hippocampal synaptic plasticity and hippocampus-dependent memory? J Neurosci 23(15):6304-14. [PubMed: 12867515]  [MGI Ref ID J:84481]

Blendy JA; Kaestner KH; Schmid W; Gass P; Schutz G. 1996. Targeting of the CREB gene leads to up-regulation of a novel CREB mRNA isoform. EMBO J 15(5):1098-106. [PubMed: 8605879]  [MGI Ref ID J:31886]

Blendy JA; Schmid W; Kiessling M; Schutz G; Gass P. 1995. Effects of kainic acid induced seizures on immediate early gene expression in mice with a targeted mutation of the CREB gene. Brain Res 681(1-2):8-14. [PubMed: 7552295]  [MGI Ref ID J:26212]

Bourtchuladze R; Frenguelli B; Blendy J; Cioffi D; Schutz G; Silva AJ. 1994. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79(1):59-68. [PubMed: 7923378]  [MGI Ref ID J:20672]

Briand LA; Blendy JA. 2013. Not all stress is equal: CREB is not necessary for restraint stress reinstatement of cocaine-conditioned reward. Behav Brain Res 246:63-8. [PubMed: 23458740]  [MGI Ref ID J:197560]

Briand LA; Vassoler FM; Pierce RC; Valentino RJ; Blendy JA. 2010. Ventral tegmental afferents in stress-induced reinstatement: the role of cAMP response element-binding protein. J Neurosci 30(48):16149-59. [PubMed: 21123561]  [MGI Ref ID J:166747]

Cho YH; Giese KP; Tanila H; Silva AJ; Eichenbaum H. 1998. Abnormal hippocampal spatial representations in alphaCaMKIIT286A and CREBalphaDelta- mice. Science 279(5352):867-9. [PubMed: 9452387]  [MGI Ref ID J:45751]

Conti AC; Cryan JF; Dalvi A; Lucki I; Blendy JA. 2002. cAMP response element-binding protein is essential for the upregulation of brain-derived neurotrophic factor transcription, but not the behavioral or endocrine responses to antidepressant drugs. J Neurosci 22(8):3262-8. [PubMed: 11943827]  [MGI Ref ID J:76150]

Gass P; Wolfer DP; Balschun D; Rudolph D; Frey U; Lipp HP; Schutz G. 1998. Deficits in memory tasks of mice with CREB mutations depend on gene dosage Learn Mem 5(4-5):274-88. [PubMed: 10454354]  [MGI Ref ID J:51148]

Glazewski S; Barth AL; Wallace H; McKenna M; Silva A; Fox K. 1999. Impaired experience-dependent plasticity in barrel cortex of mice lacking the alpha and delta isoforms of CREB. Cereb Cortex 9(3):249-56. [PubMed: 10355905]  [MGI Ref ID J:101994]

Graves L; Dalvi A; Lucki I; Blendy JA; Abel T. 2002. Behavioral analysis of CREB alphadelta mutation on a B6/129 F1 hybrid background. Hippocampus 12(1):18-26. [PubMed: 11918283]  [MGI Ref ID J:113304]

Graves LA; Hellman K; Veasey S; Blendy JA; Pack AI; Abel T. 2003. Genetic evidence for a role of CREB in sustained cortical arousal. J Neurophysiol 90(2):1152-9. [PubMed: 12711709]  [MGI Ref ID J:103027]

Gur TL; Conti AC; Holden J; Bechtholt AJ; Hill TE; Lucki I; Malberg JE; Blendy JA. 2007. cAMP response element-binding protein deficiency allows for increased neurogenesis and a rapid onset of antidepressant response. J Neurosci 27(29):7860-8. [PubMed: 17634380]  [MGI Ref ID J:123315]

Hebda-Bauer EK; Luo J; Watson SJ; Akil H. 2007. Female CREBalphadelta- deficient mice show earlier age-related cognitive deficits than males. Neuroscience 150(2):260-72. [PubMed: 18029102]  [MGI Ref ID J:130757]

Hebda-Bauer EK; Watson SJ; Akil H. 2004. CREB deficient mice show inhibition and low activity in novel environments without changes in stress reactivity. Eur J Neurosci 20(2):503-13. [PubMed: 15233759]  [MGI Ref ID J:100343]

Hebda-Bauer EK; Watson SJ; Akil H. 2005. Cognitive performance is highly sensitive to prior experience in mice with a learning and memory deficit: failure leads to more failure. Learn Mem 12(5):461-71. [PubMed: 16166394]  [MGI Ref ID J:114429]

Hummler E; Cole TJ; Blendy JA; Ganss R; Aguzzi A; Schmid W; Beermann F; Schutz G. 1994. Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors. Proc Natl Acad Sci U S A 91(12):5647-51. [PubMed: 8202542]  [MGI Ref ID J:18749]

Jin SH; Blendy JA; Thomas SA. 2005. Cyclic AMP response element-binding protein is required for normal maternal nurturing behavior. Neuroscience 133(3):647-55. [PubMed: 15893884]  [MGI Ref ID J:104253]

Josselyn SA; Kida S; Silva AJ. 2004. Inducible repression of CREB function disrupts amygdala-dependent memory. Neurobiol Learn Mem 82(2):159-63. [PubMed: 15341801]  [MGI Ref ID J:128870]

Kogan JH; Frankland PW; Blendy JA; Coblentz J; Marowitz Z; Schutz G; Silva AJ.. 1997. Spaced training induces normal long-term memory in CREB mutant mice. Curr Biol 7(1):1-11. [PubMed: 8999994]  [MGI Ref ID J:38651]

Li L; Howell K; Sands M; Banahan M; Frohlich S; Rowan SC; Neary R; Ryan D; McLoughlin P. 2013. The alpha and Delta isoforms of CREB1 are required to maintain normal pulmonary vascular resistance. PLoS One 8(12):e80637. [PubMed: 24349008]  [MGI Ref ID J:211156]

Maldonado R; Blendy JA; Tzavara E; Gass P; Roques BP; Hanoune J; Schutz G. 1996. Reduction of morphine abstinence in mice with a mutation in the gene encoding CREB [see comments] Science 273(5275):657-9. [PubMed: 8662559]  [MGI Ref ID J:34605]

Pandey SC; Roy A; Zhang H; Xu T. 2004. Partial deletion of the cAMP response element-binding protein gene promotes alcohol-drinking behaviors. J Neurosci 24(21):5022-30. [PubMed: 15163695]  [MGI Ref ID J:96876]

Parlato R; Cruz H; Otto C; Murtra P; Parkitna JR; Martin M; Bura SA; Begus-Nahrmann Y; von Bohlen und Halbach O; Maldonado R; Schutz G; Luscher C. 2010. Effects of the cell type-specific ablation of the cAMP-responsive transcription factor in noradrenergic neurons on locus coeruleus firing and withdrawal behavior after chronic exposure to morphine. J Neurochem 115(3):563-73. [PubMed: 20367754]  [MGI Ref ID J:165910]

Parlato R; Otto C; Begus Y; Stotz S; Schutz G. 2007. Specific ablation of the transcription factor CREB in sympathetic neurons surprisingly protects against developmentally regulated apoptosis. Development 134(9):1663-70. [PubMed: 17376811]  [MGI Ref ID J:121244]

Pham TA; Rubenstein JL; Silva AJ; Storm DR; Stryker MP. 2001. The CRE/CREB pathway is transiently expressed in thalamic circuit development and contributes to refinement of retinogeniculate axons. Neuron 31(3):409-20. [PubMed: 11516398]  [MGI Ref ID J:71120]

Riccio A; Alvania RS; Lonze BE; Ramanan N; Kim T; Huang Y; Dawson TM; Snyder SH; Ginty DD. 2006. A nitric oxide signaling pathway controls CREB-mediated gene expression in neurons. Mol Cell 21(2):283-94. [PubMed: 16427017]  [MGI Ref ID J:166020]

Rudiger R; Binder E; Tsarovina K; Schmidt M; Reiff T; Stubbusch J; Rohrer H. 2009. In vivo role for CREB signaling in the noradrenergic differentiation of sympathetic neurons. Mol Cell Neurosci 42(2):142-51. [PubMed: 19545628]  [MGI Ref ID J:154244]

Sekeres MJ; Neve RL; Frankland PW; Josselyn SA. 2010. Dorsal hippocampal CREB is both necessary and sufficient for spatial memory. Learn Mem 17(6):280-3. [PubMed: 20495061]  [MGI Ref ID J:185932]

Shim JH; Greenblatt MB; Singh A; Brady N; Hu D; Drapp R; Ogawa W; Kasuga M; Noda T; Yang SH; Lee SK; Rebel VI; Glimcher LH. 2012. Administration of BMP2/7 in utero partially reverses Rubinstein-Taybi syndrome-like skeletal defects induced by Pdk1 or Cbp mutations in mice. J Clin Invest 122(1):91-106. [PubMed: 22133875]  [MGI Ref ID J:184575]

Walters CL; Blendy JA. 2001. Different requirements for cAMP response element binding protein in positive and negative reinforcing properties of drugs of abuse. J Neurosci 21(23):9438-44. [PubMed: 11717377]  [MGI Ref ID J:123425]

Walters CL; Cleck JN; Kuo YC; Blendy JA. 2005. Mu-opioid receptor and CREB activation are required for nicotine reward. Neuron 46(6):933-43. [PubMed: 15953421]  [MGI Ref ID J:99851]

Walters CL; Godfrey M; Li X; Blendy JA. 2005. Alterations in morphine-induced reward, locomotor activity, and thermoregulation in CREB-deficient mice. Brain Res 1032(1-2):193-9. [PubMed: 15680959]  [MGI Ref ID J:95568]

Walters CL; Kuo YC; Blendy JA. 2003. Differential distribution of CREB in the mesolimbic dopamine reward pathway. J Neurochem 87(5):1237-44. [PubMed: 14622103]  [MGI Ref ID J:125995]

Xu W; Kasper LH; Lerach S; Jeevan T; Brindle PK. 2007. Individual CREB-target genes dictate usage of distinct cAMP-responsive coactivation mechanisms. EMBO J 26(12):2890-903. [PubMed: 17525731]  [MGI Ref ID J:122605]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryThe resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 7 generations. In heterozygote crosses, the number of homozygous progeny born (15%) does not reach the expected Mendelian ratio indicating low survival of homozygous embryos. The strain is maintained as a heterozygote.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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