Overview

This strain is currently unavailable due to replenishing of cryopreserved stocks. Interested customers can register interest.

These double mutant mice express the human Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide, (FCER1A), under the control of the human FCER1A promoter and carry the Fcer1a^tm1Knt targeted mutation. Mice that are hemizygous for the transgene and homozygous for the targeted mutation respond to experimental induction of anaphylaxis and are more sensitive to 2,4,6-tri-nitrobenzenesulfonic acid (TNBS)-induced colitis. These mutant mice exhibit increased levels of IL4 in the colon, enhanced intestinal permeability and modified fecal bacterial flora composition. This mutant mouse strain may be useful in studies of allergic response, anaphylaxis, hypersensitive immune response, and inflammatory bowel disease.

Donating Investigator

Jean-Pierre Kinet, Beth Israel Deaconess Medical Center

Genetic overview

Genetic Background	Generation

Fcer1a^tm1Knt

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Fcer1a	Fc receptor, IgE, high affinity I, alpha polypeptide

Tg(FCER1A)1Bhk

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

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Research Applications

Immunology, Inflammation and Autoimmunity Research

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Details

Detailed Description

These double mutant mice express the human Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide, (FCER1A), under the control of the human FCER1A promoter and carry the Fcer1a^tm1Knt targeted mutation. Mice that are hemizygous for the transgene and homozygous for the targeted mutation express a functioning chimeric receptor complex in which the human alpha-chain associates with the mouse beta- and gamma- chains. Transgene expression is detected on bone marrow derived cultured mast cells (BMMC), mast cells, basophils, monocytes, eosinophils, and epidermal Langerhans cells by FACS, hIgE binding and Western blot analysis and mimics both the human FCER1A expression and cell specificity pattern. The humanized receptor is estimated to be expressed approximately 3 to 5 fold higher than the endogenous mouse receptor. The double mutant mice respond to experimental induction of anaphylaxis and are more sensitive to 2,4,6-tri-nitrobenzenesulfonic acid (TNBS)-induced colitis. These mutant mice exhibit increased levels of IL4 in the colon, enhanced intestinal permeability and modified fecal bacterial flora composition. This mutant mouse strain may be useful in studies of allergic response, anaphylaxis, hypersensitive immune response, and inflammatory bowel disease.

Development

These double mutant mice were generated by crossing transgenic mice carrying the Tg(FCER1A)1Bhk transgene with Fcer1a^tm1Knt targeted mutant mice. The targeted mutant allele was created using a targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes to disrupt exon 4, which encodes an immunoglobulin domain. The construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to BALB/cJ mice, and then backcrossed to the same for 20 generations.

The transgenic strain was generated using a transgenic construct containing the entire human Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide, (FCER1A), including 2.9kb of upstream sequence. The transgene was coinjected with a plasmid containing the hprt minigene. These constructs were transfected into ES65-154 (E14TG2a-165) embryonic stem (ES). ES cells containing the construct were injected into recipient C57BL/6 blastocysts to generate chimeric mice. The resulting male chimeric animals were bred to female mice carrying the Fcer1a^tm1Knt targeted mutation. The donating investigator reported that double mutant mice were then backcrossed to C57BL/6 (see SNP note below) for more than 8 generations before arriving at The Jackson Laboratory.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Expression Data

Expressed Gene	FCER1A, Fc fragment of IgE receptor Ia, human
Site of Expression

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Dombrowicz D; Brini AT; Flamand V; Hicks E; Snouwaert JN; Kinet JP; Koller BH. 1996. Anaphylaxis mediated through a humanized high affinity IgE receptor. J Immunol 157(4):1645-51PubMed: 8759751 MGI: J:113572

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Genetics

Fcer1a^tm1Knt

Allele Symbol: Fcer1a^tm1Knt

Allele Name	targeted mutation 1, Jean-Pierre Kinet
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Fc epsilon RI alpha chain-; FcepsilonR1alpha^-; FcepsilonRI^-; Fcer1a^-; Fcer1a^tm1Rav; FcerIa^-
Gene Symbol and Name	Fcer1a, Fc receptor, IgE, high affinity I, alpha polypeptide
Gene Synonym(s)
Strain of Origin	129
Chromosome	1
General Note	ES cell line = D3 (129S2/SvPas) or E14TG2a (129P2/OlaHsd).
Molecular Note	Exon 4, encoding an immunoglobulin domain, was disrupted by the insertion of a neomycin selection cassette. The absence of a functional encoded protein on the cell surface was determined by fluorescence activated cell sorting analysis of bone marrow mast cells obtained from homozygous mutant mice.
Mutations Made By	Devin Turner, Beth Israel Deaconess Medical Center

Tg(FCER1A)1Bhk

Allele Symbol: Tg(FCER1A)1Bhk

Allele Name	transgene insertion 1, Beverly H Koller
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	hFcepsilonR1alpha^- hFcepsilonR1alpha+; hFcepsilonR1alphaTg
Gene Symbol and Name	Tg(FCER1A)1Bhk, transgene insertion 1, Beverly H Koller
Gene Synonym(s)
Promoter	FCER1A, Fc fragment of IgE receptor Ia, human
Expressed Gene	FCER1A, Fc fragment of IgE receptor Ia, human
Strain of Origin	129P2/OlaHsd
Chromosome	UN
General Note	ES cells = ES65-154 (E14TG2a-165) cells
Molecular Note	The transgenic construct contains the entire human Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide, (FCER1A), including 2.9kb of upstream sequence. The transgene was coinjected with a plasmid containing the hprt minigene. These constructs were transfected into ES65-154 (E14TG2a-165) embryonic stem (ES).

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
- Inflammation
  - Inflammatory bowel disease

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Fcer1a^tm1Knt/Fcer1a^tm1Knt Tg(FCER1A)1Bhk/?
B6.129-Fcer1a Tg(FCER1A)1Bhk

hematopoietic system phenotype

abnormal macrophage physiology
- macrophages secrete higher levels of TNF in response to IgE complexes compared to controls

immune system phenotype

abnormal macrophage physiology
- macrophages secrete higher levels of TNF in response to IgE complexes compared to controls

increased tumor necrosis factor secretion
- macrophages secrete higher levels of TNF in response to IgE complexes compared to controls

References

Dombrowicz D; Brini AT; Flamand V; Hicks E; Snouwaert JN; Kinet JP; Koller BH. 1996. Anaphylaxis mediated through a humanized high affinity IgE receptor. J Immunol 157(4):1645-51PubMed: 8759751 MGI: J:113572

Additional - Fcer1a^tm1Knt related

Additional - Tg(FCER1A)1Bhk related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Tg(FCER1A)1Bhk
- Separated PCR:Fcer1aalternate2
- Separated PCR:Fcer1aalternate2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these double mutant mice may be bred as hemizygous for the transgene and homozygous for the targeted mutation.
- Additional Breeding and Husbandry Support
Citation
When using the B6.Cg-Fcer1a^tm1Knt Tg(FCER1A)1Bhk/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010506 in your Materials and Methods section.

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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

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Fcer1atm1Knt

Allele Symbol: Fcer1atm1Knt

Tg(FCER1A)1Bhk

Allele Symbol: Tg(FCER1A)1Bhk

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Fcer1atm1Knt/Fcer1atm1Knt Tg(FCER1A)1Bhk/?B6.129-Fcer1a Tg(FCER1A)1Bhk

hematopoietic system phenotype

immune system phenotype

References

Additional - Fcer1atm1Knt related

Additional - Tg(FCER1A)1Bhk related

Genotyping Protocols

Breeding Considerations

Citation

Strain Interest Registration

Contact Information

Interest

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Fcer1a^tm1Knt

Allele Symbol: Fcer1a^tm1Knt

Genotype: Fcer1a^tm1Knt/Fcer1a^tm1Knt Tg(FCER1A)1Bhk/?
B6.129-Fcer1a Tg(FCER1A)1Bhk

Additional - Fcer1a^tm1Knt related