Overview

These Gab2 knockout mice exhibit an impaired mast cell response (degranulation, cytokine expression), a diminished allergic response, reduced mast cell numbers and reduced passive cutaneous and systemic anaphylaxis. This mutant mouse strain may be useful in studies of allergic reactions and anaphylaxis.

Donating Investigator

Benjamin Neel, NYU School of Medicine

Genetic overview

Genetic Background	Generation

Gab2^tm1Hhg

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Gab2	growth factor receptor bound protein 2-associated protein 2

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Research Applications

Hematological Research
Immunology, Inflammation and Autoimmunity Research
Research Tools

View All Research Applications

Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Mast cell response (degranulation, cytokine expression) to stimulation of the IgE receptor FceR1 is impaired and results in a diminished allergic response. Passive cutaneous and systemic anaphylaxis is significantly reduced in these mice. Mast cell numbers are reduced in back and thigh skin and undetectable in the peritoneum.

This mutant mouse strain may be useful in studies of allergic reactions and anaphylaxis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing a loxP-flanked SA beta gal PGKneo cassette was used to replace exon 1. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to BALB/c mice for 20 generations. Upon arrival at The Jackson Laboratory, mutant mice were bred to BALB/cJ inbred mice to establish the colony.

Expression Data

Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression

Control Suggestions

000651 BALB/cJ

Additional Information

Considerations for Choosing Controls

Selected References

Gu H; Saito K; Klaman LD; Shen J; Fleming T; Wang Y; Pratt JC; Lin G; Lim B; Kinet JP; Neel BG. 2001. Essential role for Gab2 in the allergic response. Nature 412(6843):186-90PubMed: 11449275 MGI: J:70424

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Genetics

Gab2^tm1Hhg

Allele Symbol: Gab2^tm1Hhg

Allele Name	targeted mutation 1, Haihua Gu
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	Gab2^-
Gene Symbol and Name	Gab2, growth factor receptor bound protein 2-associated protein 2
Gene Synonym(s)
Expressed Gene	lacZ, beta-galactosidase, E. coli
Strain of Origin	129S4/SvJae
Chromosome	7
Molecular Note	Exon 1 was replaced with an SA-lacZ-PGK-neo cassette via homologous recombination. Protein product was undetectable in various tissues from homozygous mutant animals as determined by Western blot analysis.
Mutations Made By	Benjamin Neel, NYU School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Hematological Research
- Mast Cell Deficiency
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - Mast Cell Deficiency
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - Mast Cell Deficiency

Mammalian Phenotype Terms by Genotype

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

Genotype: Gab2^tm1Hhg/Gab2^tm1Hhg
involves: 129S4/SvJae

mammalian phenotype

immune system phenotype
- Normal - lymphocyte development is normal

hematopoietic system phenotype

decreased mast cell number
- Normal - however, ear skin mast cell numbers are normal
- mast cell numbers in back and thigh skin are reduced 30% to 50% compared to in wild-type mice whereas peritoneal mast cells are undetectable

decreased mast cell degranulation
- Normal - however, TPA plus ionomycin-induced degranulation is normal
- Fcer1a-stimulated bone marrow-derived mast cells exhibit reduced serotonin release compared with similarly treated wild-type cells

immune system phenotype

decreased mast cell number
- mast cell numbers in back and thigh skin are reduced 30% to 50% compared to in wild-type mice whereas peritoneal mast cells are undetectable
- Normal - however, ear skin mast cell numbers are normal

decreased mast cell degranulation
- Normal - however, TPA plus ionomycin-induced degranulation is normal
- Fcer1a-stimulated bone marrow-derived mast cells exhibit reduced serotonin release compared with similarly treated wild-type cells

decreased susceptibility to type I hypersensitivity reaction
- passive cutaneous and systemic anaphylaxis are reduced compared to in similarly treated wild-type mice

References

Gu H; Saito K; Klaman LD; Shen J; Fleming T; Wang Y; Pratt JC; Lin G; Lim B; Kinet JP; Neel BG. 2001. Essential role for Gab2 in the allergic response. Nature 412(6843):186-90PubMed: 11449275 MGI: J:70424

Additional - Gab2^tm1Hhg related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Gab2
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the C.129S4-Gab2^tm1Hhg/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32100 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

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

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Gab2tm1Hhg

Allele Symbol: Gab2tm1Hhg

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Gab2tm1Hhg/Gab2tm1Hhginvolves: 129S4/SvJae

mammalian phenotype

hematopoietic system phenotype

immune system phenotype

References

Additional - Gab2tm1Hhg related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Gab2^tm1Hhg

Allele Symbol: Gab2^tm1Hhg

Genotype: Gab2^tm1Hhg/Gab2^tm1Hhg
involves: 129S4/SvJae

Additional - Gab2^tm1Hhg related