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| 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 Fcer1atm1Knt 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. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Congenic; Targeted Mutation; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Donating Investigator Jean-Pierre Kinet, Beth Israel Deaconess Medical Center 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 Fcer1atm1Knt 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 Fcer1atm1Knt 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 Fcer1atm1Knt 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.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Fcer1atm1Knt allele
010512 B6.129S2(Cg)-Fcer1atm1Knt/J 005629 C.129S2-Fcer1atm1Knt/J View Strains carrying Fcer1atm1Knt (2 strains)
Phenotype
Phenotype Information
assigned by genotype
Fcer1atm1Knt/Fcer1atm1Knt Tg(FCER1A)1Bhk/?
B6.129-Fcer1atm1Knt Tg(FCER1A)1Bhk
- immune system phenotype
- abnormal macrophage physiology
- macrophages secrete higher levels of TNF in response to IgE complexes compared to controls (MGI Ref ID J:144620)
- increased tumor necrosis factor secretion
- macrophages secrete higher levels of TNF in response to IgE complexes compared to controls (MGI Ref ID J:144620)
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
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Fcer1atm1Knt | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Jean-Pierre Kinet | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Fc epsilon RI alpha chain-; FcepsilonR1alpha-; FcepsilonRI-; Fcer1a-; Fcer1atm1Rav; FcerIa-; | ||
| Mutation Made By | Devin Turner, Beth Israel Deaconess Medical Center | ||
| Strain of Origin | 129 | ||
| ES Cell Line Name | Other (see notes) | ||
| ES Cell Line Strain | 129 | ||
| Gene Symbol and Name | Fcer1a, Fc receptor, IgE, high affinity I, alpha polypeptide | ||
| Chromosome | 1 | ||
| Gene Common Name(s) | FCE1A; Fc epsilon high affinity receptor alpha; FcERI; Fce1a; Fcr-5; Iger01; RATIGER01; | ||
| 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 mastcells obtained from homozygous mutant mice. [MGI Ref ID J:39250] | ||
| Allele Symbol | Tg(FCER1A)1Bhk | ||
| Allele Name | transgene insertion 1, Beverly H Koller | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | hFcepsilonR1alpha- hFcepsilonR1alpha+; hFcepsilonR1alphaTg; | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | Other (see notes) | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Expressed Gene | FCER1A, Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide, human | ||
| Promoter | FCER1A, Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide, human | ||
| 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). [MGI Ref ID J:113572] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Fcer1atm1Kntalternate2,SEPARATED MELT
Tg(FCER1A)1Bhk, Standard PCR
Fcer1atm1Kntalternate2, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
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):1645-51. [PubMed: 8759751] [MGI Ref ID J:113572]
Additional References
Fcer1atm1Knt relatedTg(FCER1A)1Bhk relatedAbboud G; Staumont-Salle D; Kanda A; Roumier T; Deruytter N; Lavogiez C; Fleury S; Remy P; Papin JP; Capron M; Dombrowicz D. 2009. Fc(epsilon)RI and FcgammaRIII/CD16 differentially regulate atopic dermatitis in mice. J Immunol 182(10):6517-26. [PubMed: 19414806] [MGI Ref ID J:148317]
Albanesi M; Mancardi DA; Macdonald LE; Iannascoli B; Zitvogel L; Murphy AJ; Leusen JH; Bruhns P. 2012. Cutting Edge: FcgammaRIII (CD16) and FcgammaRI (CD64) Are Responsible for Anti-Glycoprotein 75 Monoclonal Antibody TA99 Therapy for Experimental Metastatic B16 Melanoma. J Immunol 189(12):5513-7. [PubMed: 23150715] [MGI Ref ID J:190859]
Binstadt BA; Patel PR; Alencar H; Nigrovic PA; Lee DM; Mahmood U; Weissleder R; Mathis D; Benoist C. 2006. Particularities of the vasculature can promote the organ specificity of autoimmune attack. Nat Immunol 7(3):284-92. [PubMed: 16444258] [MGI Ref ID J:112604]
Cheng LE; Wang ZE; Locksley RM. 2010. Murine B cells regulate serum IgE levels in a CD23-dependent manner. J Immunol 185(9):5040-7. [PubMed: 20870945] [MGI Ref ID J:165198]
Denzel A; Maus UA; Rodriguez Gomez M; Moll C; Niedermeier M; Winter C; Maus R; Hollingshead S; Briles DE; Kunz-Schughart LA; Talke Y; Mack M. 2008. Basophils enhance immunological memory responses. Nat Immunol 9(7):733-42. [PubMed: 18516038] [MGI Ref ID J:137679]
Dombrowicz D; Flamand V; Brigman KK; Koller BH; Kinet JP. 1993. Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor alpha chain gene. Cell 75(5):969-76. [PubMed: 8252632] [MGI Ref ID J:39250]
Dombrowicz D; Flamand V; Miyajima I; Ravetch JV; Galli SJ; Kinet JP. 1997. Absence of Fc epsilonRI alpha chain results in upregulation of Fc gammaRIII-dependent mast cell degranulation and anaphylaxis. Evidence of competition between Fc epsilonRI and Fc gammaRIII for limiting amounts of FcR beta and gamma chains. J Clin Invest 99(5):915-25. [PubMed: 9062349] [MGI Ref ID J:78651]
Dombrowicz D; Lin S; Flamand V; Brini AT; Koller BH; Kinet JP. 1998. Allergy-associated FcRbeta is a molecular amplifier of IgE- and IgG-mediated in vivo responses. Immunity 8(4):517-29. [PubMed: 9586641] [MGI Ref ID J:47138]
Dombrowicz D; Nutten S; Desreumaux P; Neut C; Torpier G; Peeters M; Colombel JF; Capron M. 2001. Role of the high affinity immunoglobulin E receptor in bacterial translocation and intestinal inflammation. J Exp Med 193(1):25-34. [PubMed: 11136818] [MGI Ref ID J:124427]
Grayson MH; Cheung D; Rohlfing MM; Kitchens R; Spiegel DE; Tucker J; Battaile JT; Alevy Y; Yan L; Agapov E; Kim EY; Holtzman MJ. 2007. Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia. J Exp Med 204(11):2759-69. [PubMed: 17954569] [MGI Ref ID J:126124]
Grimbaldeston MA; Nakae S; Kalesnikoff J; Tsai M; Galli SJ. 2007. Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat Immunol 8(10):1095-104. [PubMed: 17767162] [MGI Ref ID J:125267]
Hoffmann E; Kotsias F; Visentin G; Bruhns P; Savina A; Amigorena S. 2012. Autonomous phagosomal degradation and antigen presentation in dendritic cells. Proc Natl Acad Sci U S A 109(36):14556-61. [PubMed: 22908282] [MGI Ref ID J:189892]
Jonsson F; Mancardi DA; Kita Y; Karasuyama H; Iannascoli B; Van Rooijen N; Shimizu T; Daeron M; Bruhns P. 2011. Mouse and human neutrophils induce anaphylaxis. J Clin Invest 121(4):1484-96. [PubMed: 21436586] [MGI Ref ID J:171995]
Jonsson F; Mancardi DA; Zhao W; Kita Y; Iannascoli B; Khun H; van Rooijen N; Shimizu T; Schwartz LB; Daeron M; Bruhns P. 2012. Human FcgammaRIIA induces anaphylactic and allergic reactions. Blood 119(11):2533-44. [PubMed: 22138510] [MGI Ref ID J:182466]
Mancardi DA; Iannascoli B; Hoos S; England P; Daeron M; Bruhns P. 2008. FcgammaRIV is a mouse IgE receptor that resembles macrophage FcepsilonRI in humans and promotes IgE-induced lung inflammation. J Clin Invest 118(11):3738-50. [PubMed: 18949059] [MGI Ref ID J:144620]
Mancardi DA; Jonsson F; Iannascoli B; Khun H; Van Rooijen N; Huerre M; Daeron M; Bruhns P. 2011. The murine high-affinity IgG receptor Fc(gamma)RIV is sufficient for autoantibody-induced arthritis. J Immunol 186(4):1899-903. [PubMed: 21248252] [MGI Ref ID J:169145]
Miyajima I; Dombrowicz D; Martin TR; Ravetch JV; Kinet JP; Galli SJ. 1997. Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gammaRIII. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG1-dependent passive anaphylaxis. J Clin Invest 99(5):901-14. [PubMed: 9062348] [MGI Ref ID J:78659]
Nigro EA; Brini AT; Soprana E; Ambrosi A; Dombrowicz D; Siccardi AG; Vangelista L. 2009. Antitumor IgE adjuvanticity: key role of Fc(epsilon)RI. J Immunol 183(7):4530-6. [PubMed: 19748979] [MGI Ref ID J:152778]
Nigrovic PA; Binstadt BA; Monach PA; Johnsen A; Gurish M; Iwakura Y; Benoist C; Mathis D; Lee DM. 2007. Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. Proc Natl Acad Sci U S A 104(7):2325-30. [PubMed: 17277081] [MGI Ref ID J:119744]
Nunomura S; Kawakami Y; Kawakami T; Ra C. 2012. The FcRbeta- and gamma-ITAMs play crucial but distinct roles in the full activation of mast cells induced by IgEkappa and Protein L. J Immunol 188(8):4052-64. [PubMed: 22430736] [MGI Ref ID J:184055]
Porcherie A; Mathieu C; Peronet R; Schneider E; Claver J; Commere PH; Kiefer-Biasizzo H; Karasuyama H; Milon G; Dy M; Kinet JP; Louis J; Blank U; Mecheri S. 2011. Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria. J Exp Med 208(11):2225-36. [PubMed: 21967768] [MGI Ref ID J:178860]
Sun J; Arias K; Alvarez D; Fattouh R; Walker T; Goncharova S; Kim B; Waserman S; Reed J; Coyle AJ; Jordana M. 2007. Impact of CD40 ligand, B cells, and mast cells in peanut-induced anaphylactic responses. J Immunol 179(10):6696-703. [PubMed: 17982059] [MGI Ref ID J:154013]
Taube C; Miyahara N; Ott V; Swanson B; Takeda K; Loader J; Shultz LD; Tager AM; Luster AD; Dakhama A; Gelfand EW. 2006. The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness. J Immunol 176(5):3157-64. [PubMed: 16493075] [MGI Ref ID J:129412]
Taube C; Wei X; Swasey CH; Joetham A; Zarini S; Lively T; Takeda K; Loader J; Miyahara N; Kodama T; Shultz LD; Donaldson DD; Hamelmann EH; Dakhama A; Gelfand EW. 2004. Mast cells, Fc epsilon RI, and IL-13 are required for development of airway hyperresponsiveness after aerosolized allergen exposure in the absence of adjuvant. J Immunol 172(10):6398-406. [PubMed: 15128831] [MGI Ref ID J:89853]
Tsai M; Chen CC; Mukai K; Song CH; Thompson LJ; Ziegler SF; Tam SY; Galli SJ. 2010. Thymic stromal lymphopoietin contributes to myeloid hyperplasia and increased immunoglobulins, but not epidermal hyperplasia, in RabGEF1-deficient mice. Am J Pathol 177(5):2411-20. [PubMed: 20829437] [MGI Ref ID J:166267]
Wang J; Cheng X; Xiang MX; Alanne-Kinnunen M; Wang JA; Chen H; He A; Sun X; Lin Y; Tang TT; Tu X; Sjoberg S; Sukhova GK; Liao YH; Conrad DH; Yu L; Kawakami T; Kovanen PT; Libby P; Shi GP. 2011. IgE stimulates human and mouse arterial cell apoptosis and cytokine expression and promotes atherogenesis in Apoe-/- mice. J Clin Invest 121(9):3564-77. [PubMed: 21821913] [MGI Ref ID J:178258]
Jonsson F; Mancardi DA; Zhao W; Kita Y; Iannascoli B; Khun H; van Rooijen N; Shimizu T; Schwartz LB; Daeron M; Bruhns P. 2012. Human FcgammaRIIA induces anaphylactic and allergic reactions. Blood 119(11):2533-44. [PubMed: 22138510] [MGI Ref ID J:182466]
Mancardi DA; Iannascoli B; Hoos S; England P; Daeron M; Bruhns P. 2008. FcgammaRIV is a mouse IgE receptor that resembles macrophage FcepsilonRI in humans and promotes IgE-induced lung inflammation. J Clin Invest 118(11):3738-50. [PubMed: 18949059] [MGI Ref ID J:144620]
Nigro EA; Brini AT; Soprana E; Ambrosi A; Dombrowicz D; Siccardi AG; Vangelista L. 2009. Antitumor IgE adjuvanticity: key role of Fc(epsilon)RI. J Immunol 183(7):4530-6. [PubMed: 19748979] [MGI Ref ID J:152778]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these double mutant mice may be bred as hemizygous for the transgene and homozygous for the targeted mutation.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2450.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $3185.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering Information
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