Overview

Also Known As:CBP KO

These Crebbp knock-out mice exhibit embryonic lethality and heterozygotes show growth retardation, craniofacial abnormalities and failure to thrive. They may be useful in applications related to signal transduction pathways and studies of Rubinstein-Taybi syndrome (RTS) in humans.

Donating Investigator

Andrew L. Kung, Columbia University

Genetic overview

Genetic Background	Generation

Crebbp^tm1Dli

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Crebbp	CREB binding protein

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Research Applications

Apoptosis Research
Developmental Biology Research
Hematological Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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.

Selected References

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):361-72PubMed: 9590171 MGI: J:47301

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Genetics

Crebbp^tm1Dli

Allele Symbol: Crebbp^tm1Dli

Allele Name	targeted mutation 1, David Livingston
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	CBP^-
Gene Symbol and Name	Crebbp, CREB binding protein
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	16
Molecular Note	Replacement of two exons encoding the CH1 domain of the Crebbp gene with a neomycin cassette.
Mutations Made By	Andrew Kung, Columbia University

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Rubinstein-Taybi syndrome

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

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

Genotype: Crebbp^tm1Dli related

Apoptosis Research
- Endogenous Regulators
  - Autoimmune Lymphroliferatve syndrome
Developmental Biology Research
- Craniofacial and Palate Defects
- Embryonic Lethality (Homozygous)
- Neural Tube Defects
- Internal/Organ Defects
  - hematopoietic defects
Hematological Research
- Hematopoietic Defects
Neurobiology Research
- Neural Tube Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Crebbp^tm1Dli/Crebbp⁺
involves: 129S6/SvEvTac * C57BL/6

hematopoietic system phenotype

abnormal leukocyte morphology
- 22% of 9-12 month old mutants show leukocytes with a pseudo Pelger-Huet anomaly

decreased common myeloid progenitor cell number
- in mice with splenomegaly
- 9-12 month old mutants show a decrease in common myeloid progenitors
- mutants have fewer total colony-forming cells in the marrow than wild-type mice, most notably the granulocytic and monocytic colony-forming cells

abnormal definitive hematopoiesis
- abundance of all hematopoietic cells types is significantly diminished in mice with splenomegaly
- 2 of 14 mice at 3-4 months of age have small clusters of immature cells in the center of the marrow space, indicative of very early stages of myelodysplastic hematopoiesis
- increase in myeloid cells in mice with splenomegaly

abnormal megakaryocyte morphology
- more than 50% of 9-12 month old mutants exhibit either increased numbers of megakaryocytes or abnormal forms such as hyperlobulated cells or naked nuclei

enlarged spleen
- severe splenomegaly in 73% of 12-18 month old mice but not in young mice
- mild but significant splenomegaly in 3-4 and 9-12 month old mutants
- spleen contains an excess of myeloid and erythroid cells

decreased lymphocyte cell number
- Normal - however, leukocyte, erythrocyte and platelet numbers are normal
- lymphoid cell compartment is smaller at 9-12 months of age

abnormal common myeloid progenitor cell morphology
- mutants show an increase in Annexin V+ cells in the lineage-depleted (Lin-) fraction of the marrow enriched for stem and progenitor cells, indicating an increase in apoptosis in marrow progenitors

decreased B cell number
- in mice with splenomegaly

increased bone marrow cell number
- bone marrow is more cellular than in wild type mice when corrected for body weight at 3-4 and 9-12 months of age

increased megakaryocyte cell number

absent pre-B cells
- in mice with splenomegaly

decreased hematopoietic stem cell number
- approximate 2-fold fewer long-term hematopoietic stem cells per femur at 9-12 months of age

extramedullary hematopoiesis
- in mice with splenomegaly

abnormal granulocyte morphology
- 55% of 9-12 month old mutants show hypersegemented granulocytes

increased granulocyte number
- at 9-12 months of age

cellular phenotype

increased cellular sensitivity to gamma-irradiation
- mutants treated with a 10-Gy split-dose total body irradiation die before wild-type mice do and none survive compared to 1/3 of wild-type mice that survive, indicating increased hypersensitivity to ionizing radiation
- a lower percentage of mutants treated with a split-dose of 11 Gy total body irradiation followed by a bone marrow graft survive compared to wild-type mice treated in the same way

craniofacial phenotype

abnormal craniofacial morphology
- craniofacial abnormalities

immune system phenotype

abnormal granulocyte morphology
- 55% of 9-12 month old mutants show hypersegemented granulocytes

absent pre-B cells
- in mice with splenomegaly

decreased lymphocyte cell number
- Normal - however, leukocyte, erythrocyte and platelet numbers are normal
- lymphoid cell compartment is smaller at 9-12 months of age

enlarged spleen
- mild but significant splenomegaly in 3-4 and 9-12 month old mutants
- spleen contains an excess of myeloid and erythroid cells
- severe splenomegaly in 73% of 12-18 month old mice but not in young mice

increased granulocyte number
- at 9-12 months of age

decreased B cell number
- in mice with splenomegaly

abnormal leukocyte morphology
- 22% of 9-12 month old mutants show leukocytes with a pseudo Pelger-Huet anomaly

neoplasm

increased histiocytic sarcoma incidence

increased leukemia incidence
- myelogenous and lymphocytic leukemias

increased hemolymphoid system tumor incidence
- hematologic neoplasia in animals 1 year or older, which include histiocytic sarcomas, a tumor of hematopoietic origin, and myelogenous and lymphocytic leukemias

growth/size/body region phenotype

enlarged spleen
- spleen contains an excess of myeloid and erythroid cells
- mild but significant splenomegaly in 3-4 and 9-12 month old mutants
- severe splenomegaly in 73% of 12-18 month old mice but not in young mice

decreased body weight

postnatal growth retardation

Genotype: Crebbp^tm1Dli/Crebbp^tm1Dli
involves: 129S6/SvEvTac * C57BL/6

embryo phenotype

open neural tube

mortality/aging

embryonic lethality, complete penetrance
- die by E10.5

nervous system phenotype

open neural tube

References

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):361-72PubMed: 9590171 MGI: 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):272-7PubMed: 10673499 MGI: J:60630

Additional - Crebbp^tm1Dli related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Crebbp
- Genotyping resources and troubleshooting
Breeding Considerations

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.
- Additional Breeding and Husbandry Support
Citation
When using the CBP KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004069 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or Wild-type for Crebbp<tm1Dli>

Related Products and Services

Frozen Mouse Embryo	B6.129S6-Crebbp<tm1Dli>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S6-Crebbp<tm1Dli>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S6-Crebbp<tm1Dli>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.129S6-Crebbp<tm1Dli>/J Frozen Embryos	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:CBP KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Selected References

Crebbptm1Dli

Allele Symbol: Crebbptm1Dli

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

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

Genotype: Crebbptm1Dli related

Mammalian Phenotype Terms by Genotype

Genotype: Crebbptm1Dli/Crebbp+involves: 129S6/SvEvTac * C57BL/6

hematopoietic system phenotype

cellular phenotype

craniofacial phenotype

immune system phenotype

neoplasm

growth/size/body region phenotype

Genotype: Crebbptm1Dli/Crebbptm1Dliinvolves: 129S6/SvEvTac * C57BL/6

embryo phenotype

mortality/aging

nervous system phenotype

References

Additional References

Additional - Crebbptm1Dli related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Crebbp^tm1Dli

Allele Symbol: Crebbp^tm1Dli

Genotype: Crebbp^tm1Dli related

Genotype: Crebbp^tm1Dli/Crebbp⁺
involves: 129S6/SvEvTac * C57BL/6

Genotype: Crebbp^tm1Dli/Crebbp^tm1Dli
involves: 129S6/SvEvTac * C57BL/6

Additional - Crebbp^tm1Dli related