Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N7p   Donating Investigator Andrew Kung,   Dana-Farber Cancer Institute

Description
Mice that are homozygous null for the Crebbp gene are embryonic lethal, dying at about embryonic day 10.5 exhibiting open neural tube defects. Heterozygous mice though viable and fertile, are subject to early growth retardation, craniofacial abnormalities and often fail to thrive. Heterozygous mice are also subject to age-dependent splenomegaly and irregular hematopoiesis. By three months of age, the abundance of all hematopoietic cell types is significantly diminished. Older mice (10-21 months) are more prone to develop hematologic malignancies than wildtype mice.

Related Strains

Strains carrying other alleles of Crebbp

007574

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

View Strains carrying other alleles of Crebbp     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

	Leukemia, Acute Myeloid; AML - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
	Rubinstein-Taybi Syndrome; RSTS - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Crebbp^tm1Dli/Crebbp⁺

        involves: 129S6/SvEvTac * C57BL/6

• growth/size phenotype
• postnatal growth retardation (MGI Ref ID J:60630)
• craniofacial phenotype
• abnormal craniofacial morphology (MGI Ref ID J:60630)
  • craniofacial abnormalities
• tumorigenesis
• increased tumor incidence (MGI Ref ID J:60630)
  • hematologic neoplasia in animals 1 year or older, which include histiocytic sarcomas, a tumor of hematopoietic origin, and myelogenous and lymphocytic leukemias
• hematopoietic system phenotype
• abnormal hematopoiesis (MGI Ref ID J:60630)
  • abundance of all hematopoietic cells types is significantly diminished in mice with splenomegaly
  • increase in myeloid cells in mice with splenomegaly
• absent common myeloid progenitor cells (MGI Ref ID J:60630)
  • in mice with splenomegaly
• decreased B cell number (MGI Ref ID J:60630)
  • in mice with splenomegaly
• absent pre-B cells (MGI Ref ID J:60630)
  • in mice with splenomegaly
• extramedullary hematopoiesis (MGI Ref ID J:60630)
  • in mice with splenomegaly
• decreased bone marrow cell number (MGI Ref ID J:60630)
• absent common myeloid progenitor cells (MGI Ref ID J:60630)
  • in mice with splenomegaly
• enlarged spleen (MGI Ref ID J:60630)
  • severe splenomegaly in 73% of 12-18 month old mice but not in young mice
  • spleen contains an excess of myeloid and erythroid cells
• immune system phenotype
• decreased B cell number (MGI Ref ID J:60630)
  • in mice with splenomegaly
• absent pre-B cells (MGI Ref ID J:60630)
  • in mice with splenomegaly
• enlarged spleen (MGI Ref ID J:60630)
  • severe splenomegaly in 73% of 12-18 month old mice but not in young mice
  • spleen contains an excess of myeloid and erythroid cells

Crebbp^tm1Dli/Crebbp^tm1Dli

        involves: 129S6/SvEvTac * C57BL/6

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:60630)
  • die by E10.5
• nervous system phenotype
• open neural tube (MGI Ref ID J:60630)

View Research Applications

Research Applications

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

Crebbp^tm1Dli related

Apoptosis Research
Endogenous Regulators (Autoimmune Lymphroliferatve syndrome)

Developmental Biology Research
Craniofacial and Palate Defects
Embryonic Lethality (Homozygous)
Internal/Organ Defects (hematopoietic defects)
Neural Tube Defects

Hematological Research
Hematopoietic Defects

Neurobiology Research
Neural Tube Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Crebbptm1Dli
Allele Name		targeted mutation 1, David Livingston
Allele Type		Targeted (knock-out)
Common Name(s)		CBP+/-; CBP-/-;
Mutation Made By		Andrew Kung,   Dana-Farber Cancer Institute
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Crebbp, CREB binding protein
Chromosome		16
Gene Common Name(s)		AW558298; CBP; CBP/p300; KAT3A; RSTS; expressed sequence AW558298; p300/CBP;
Molecular Note		Replacement of two exons encoding the CH1 domain of the Crebbp gene with a neomycin cassette. [MGI Ref ID J:60630]

Genotyping

Genotyping Information

Genotyping Protocols

Crebbp^tm1Dli, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Yao TP; Oh SP; Fuchs M; Zhou ND; Ch'ng LE; Newsome D; Bronson RT ; Li E ; Livingston DM ; Eckner R. 1998. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93(3):361-72. [PubMed: 9590171]  [MGI Ref ID J:47301]

Additional References

Kung AL; Rebel VI; Bronson RT; Ch'ng LE; Sieff CA; Livingston DM; Yao TP. 2000. Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP. Genes Dev 14(3):272-7. [PubMed: 10673499]  [MGI Ref ID J:60630]

Crebbp^tm1Dli related

Kung AL; Rebel VI; Bronson RT; Ch'ng LE; Sieff CA; Livingston DM; Yao TP. 2000. Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP. Genes Dev 14(3):272-7. [PubMed: 10673499]  [MGI Ref ID J:60630]

Lee J; Hagerty S; Cormier KA; Kim J; Kung AL; Ferrante RJ; Ryu H. 2008. Monoallele deletion of CBP leads to pericentromeric heterochromatin condensation through ESET expression and histone H3 (K9) methylation. Hum Mol Genet 17(12):1774-82. [PubMed: 18319327]  [MGI Ref ID J:135828]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry

Heterozygous mutant females are often unable to sustain entire litters successfully, usually to the detriment of mutant pups. Heterozygous pups are smaller than wild type and often fail to thrive. To increase the likelihood of mutant pup survival when utilizing mutant females for breeding, the donating investigator suggests removing wild type littermates shortly after birth. Alternatively, these problems can be avoided by breeding male mutants to wildtype females.

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.

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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Ordering and Purchasing Information

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Contact Information
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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

OncoMouse^® requires a license from DuPont, see Licenses for Strains with OncoMouse^® Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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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