Description

Strain Information

Former Names CREB-    (Changed: 15-DEC-04 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Alcino 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

Related Strains

Strains carrying other alleles of Creb1

004995

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

View Strains carrying other alleles of Creb1     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Research Applications

Research Applications

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

Creb1^tm1Gsc related

Developmental Biology Research
Embryonic Lethality (Homozygous) (incomplete)

Neurobiology Research
Behavioral and Learning Defects

Currently there is no phenotype information for this strain.

Genes & Alleles

Gene & Allele Information

Allele Symbol		Creb1tm1Gsc
Allele Name		targeted mutation 1, Gunther Schutz
Allele Type		Targeted (knock-out)
Common Name(s)		CREB -; CREBalphadelta-; CREBalphadelta; CREBalphadelta;
Mutation Made By		Maress Lacuesta,   University of California, Los Angeles
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/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; MGC9284; 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

Creb1^tm1Gsc, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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]

Additional References

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]

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]

Creb1^tm1Gsc 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]

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]

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]

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]

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

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	The 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.
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

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