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; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N20pN1 Generation Definitions   Donating Investigator Jean-Pierre Kinet,   Beth Israel Deaconess Medical Center

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. Cultured bone marrow-derived mast cells from homozygotes, that have been activated with interleukin-3, do not bind to monomeric IgE as analyzed by flow cytometry. Mice homozygous for the mutant allele are resistant to IgE induced passive cutaneous and systemic anaphylaxis and are more susceptible to IgG1-dependent passive and active systemic anaphylaxis treatments. This mutant mouse strain may be useful in studies of anaphylaxis, and immunological response to allergens.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used 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.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Fcer1a^tm1Knt allele

010512	B6.129S2(Cg)-Fcer1atm1Knt/J
010506	B6.Cg-Fcer1atm1Knt Tg(FCER1A)1Bhk/J

View Strains carrying   Fcer1a^tm1Knt     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Fcer1a^tm1Knt/Fcer1a^tm1Knt

        either: (involves: 129 * C57BL/6) or (involves: 129 * C57BL/6 * DBA/2)

• immune system phenotype
• abnormal mast cell physiology
  • mast cells stimulated with DNP-HSA after incubation with anti-DNP IgE do not release serotonin to the same extent as wild-type mice which release 40% of total cellular serotonin   (MGI Ref ID J:39250)
• decreased susceptibility to type I hypersensitivity reaction
  • anaphylactic response as measured by a decrease in rectal temperature is almost eliminated in mutants upon treatment with anti-DNP IgE-Ab and DNP whereas controls show a significant temperature drop   (MGI Ref ID J:113572)
  • cutaneous anaphylaxis, induced in a model where ear injection of anti-DNP IgE is followed by treatment 20 hours later with DNP-HSA, is prevented in mutants compared to wild-type   (MGI Ref ID J:39250)
  • fibrinogen/fibrin deposits in ear of wild-type mice is 2-fold larger than in untreated control ear whereas no difference is observed between ears in mutants; cross-linked fibrin in treated ear is 4- to 5-fold greater in amount than in control ear in wild type mice   (MGI Ref ID J:39250)
  • mutants are resistant to induced systemic anaphylaxis; wild-type mice show a significant drop in body temperature as well as tachycardia, piloerection, and prostration after antigen challenge 24 hours following anti-DNP IgE injection; mutants have absence of any symptoms   (MGI Ref ID J:39250)
  • mutant mice do not show extravasation of dye in this model, compared to marked occurrence in feet and ears of wild-type   (MGI Ref ID J:39250)

Fcer1a^tm1Knt/Fcer1a^tm1Knt

        involves: 129 * BALB/c

• homeostasis/metabolism phenotype
• reduced thrombolysis
  • after stimulation with 2.4G2, the bone marrow mast cell degranulation response releases 35% of total cell granule content   (MGI Ref ID J:47138)
• immune system phenotype
• abnormal mast cell physiology
  • decreased mast cell degranulation relative to controls but extensive none the less   (MGI Ref ID J:78659)
• increased susceptibility to type I hypersensitivity reaction
  • active anaphylaxis induced by OVA challenge in sensitized cells   (MGI Ref ID J:78659)
  • tachycardia is prolonged   (MGI Ref ID J:78659)
  • reduction in lung conductance is prolonged   (MGI Ref ID J:78659)
  • greater reduction of dynamic compliance in lungs   (MGI Ref ID J:78659)
  • IgG1 dependent passive systemic anaphylaxis occurs   (MGI Ref ID J:78659)

View Research Applications

Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      Mast Cell Deficiency
Immunodeficiency Associated with Other Defects
Inflammation

Research Tools
Immunology and Inflammation Research
      Mast Cell Deficiency

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]

Genotyping

Genotyping Information

Genotyping Protocols

Fcer1a^tm1Kntalternate2,

SEPARATED MELT

Fcer1a^tm1Kntalternate2, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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]

Additional References

Fcer1a^tm1Knt related

Abboud 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; 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]

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]

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 mice are bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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