Description

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. Mating System Homozygote x Homozygote         (Female x Male)   06-MAY-06 Species laboratory mouse Generation N15+N1F12 (29-JUN-11) Generation Definitions   Donating Investigator Craig Gerard,   Childrens' Hospital Boston, Harvard MS

Description
Mice homozygous for the targeted mutation are viable, fertile, normal in size, and do not display any behavioral abnormalities when maintained under barrier conditions. No transcripts from the targeted gene are detected in bone marrow. Homozygous mice have normal T and B cell development but elevated IgG1 and decreased IgG2a, IgG3, and IgA in serum. In standard models of airway hyperresponsiveness (intraperitoneal (i.p.) sensitization followed by aerosol challenge), mutant mice are protected from allergic airway disease. Following epicutaneous, but not i.p., sensitization, homozygotes have significantly greater serum IgG1, dermal eosinophilia, and splenocyte Th2 cytokine secretion. Antigen presenting cells from null mice induce stronger Th2 responses. This mutant may be suitable for use in studies related to asthma, allergic skin disease, T helper cell polarization/B cell isotype switching, and other Th2- and innate-immunity studies.

Development
A targeting vector was designed to replace 736 base pairs of the N-terminal region of the targeted gene (including the start codon) with a mouse phosphoglycerate kinase promoter driven neomycin resistance gene. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were backcrossed to BALB/cAnNCrl females. Heterozygotes were mated to BALB/cAnNCrl mice for 15 generations before arriving at The Jackson Laboratory. Upon arrival, mutants were bred to BALB/cJ mice for one generation. The resulting heterozygotes were bred together to create a homozygous colony.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls

Additional Web Information

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

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.

C3ar1^tm1Cge/C3ar1^tm1Cge

        involves: 129S4/SvJae * BALB/c

• mortality/aging
• *normal* mortality/aging
  • homozygotes are obtained at the expected Mendelian ratios, are fertile and display no gross developmental or morphological defects when raised under SPF conditions   (MGI Ref ID J:64378)
• respiratory system phenotype
• decreased airway responsiveness
  • in an ovalbumin-induced model of allergic asthma, unrestrained conscious homozygotes fail to exhibit increased airway hyper-responsiveness (AHR) in response to inhaled methacholine   (MGI Ref ID J:64378)
  • similar results are obtained using the same protocol with anesthetized, mechanically ventilated homozygotes and measuring AHR in response to intravenous methacholine   (MGI Ref ID J:64378)
  • at 6 or 24 hrs after last allergen challenge, homozygotes show no significant differences in eosinophil numbers (in either BAL or lung tissue), IgE levels or BAL fluid levels of interleukin IL-4, IL-5 and IL-13 relative to wild-type mice   (MGI Ref ID J:64378)

C3ar1^tm1Cge/C3ar1^tm1Cge

        involves: 129S4/SvJae * C57BL/6

• skeleton phenotype
• decreased osteoclast cell number
  • bone marrow cells incubated with 1,25(OH)2 vitamin D3 produce fewer osteoclasts than do cells from controls   (MGI Ref ID J:166640)
• immune system phenotype
• decreased circulating interleukin-6 level
  • Il-6 production after vitamin D3 stimulation is significantly reduced   (MGI Ref ID J:166640)
• decreased osteoclast cell number
  • bone marrow cells incubated with 1,25(OH)2 vitamin D3 produce fewer osteoclasts than do cells from controls   (MGI Ref ID J:166640)
• hematopoietic system phenotype
• decreased osteoclast cell number
  • bone marrow cells incubated with 1,25(OH)2 vitamin D3 produce fewer osteoclasts than do cells from controls   (MGI Ref ID J:166640)
• homeostasis/metabolism phenotype
• decreased circulating interleukin-6 level
  • Il-6 production after vitamin D3 stimulation is significantly reduced   (MGI Ref ID J:166640)

View Research Applications

Research Applications

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

Hematological Research
Immunological Defects

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      specific complement deficiency
Inflammation
      Asthma

Research Tools
Immunology and Inflammation Research
      specific complement deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		C3ar1tm1Cge
Allele Name		targeted mutation 1, Craig Gerard
Allele Type		Targeted (knock-out)
Common Name(s)		C3aR -;
Mutation Made By		Craig Gerard,   Childrens' Hospital Boston, Harvard MS
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		C3ar1, complement component 3a receptor 1
Chromosome		6
Gene Common Name(s)		AZ3B; C3AR; HNFAG09; anaphylatoxin C3a receptor;
Molecular Note		A 736 bp DNA fragment containing the translation start site and coding sequences for the N-terminal part of the protein was replaced with a neomycin selection cassette. RT-PCR analysis on RNA derived from bone marrow cells of homozygous mice confirmed that no detectable transcript is produced from this allele. [MGI Ref ID J:64378]

Genotyping

Genotyping Information

Genotyping Protocols

C3ar1^tm1Cge, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Humbles AA; Lu B; Nilsson CA; Lilly C; Israel E; Fujiwara Y; Gerard NP; Gerard C. 2000. A role for the C3a anaphylatoxin receptor in the effector phase of asthma. Nature 406(6799):998-1001. [PubMed: 10984054]  [MGI Ref ID J:64378]

Additional References

C3ar1^tm1Cge related

Abonia JP; Friend DS; Austen WG Jr; Moore FD Jr; Carroll MC; Chan R; Afnan J; Humbles A; Gerard C; Knight P; Kanaoka Y; Yasuda S; Morokawa N; Austen KF; Stevens RL; Gurish MF. 2005. Mast cell protease 5 mediates ischemia-reperfusion injury of mouse skeletal muscle. J Immunol 174(11):7285-91. [PubMed: 15905575]  [MGI Ref ID J:98963]

Bera MM; Lu B; Martin TR; Cui S; Rhein LM; Gerard C; Gerard NP. 2011. Th17 cytokines are critical for respiratory syncytial virus-associated airway hyperreponsiveness through regulation by complement C3a and tachykinins. J Immunol 187(8):4245-55. [PubMed: 21918196]  [MGI Ref ID J:179305]

Kawamoto S; Yalcindag A; Laouini D; Brodeur S; Bryce P; Lu B; Humbles AA; Oettgen H; Gerard C; Geha RS. 2004. The anaphylatoxin C3a downregulates the Th2 response to epicutaneously introduced antigen. J Clin Invest 114(3):399-407. [PubMed: 15286806]  [MGI Ref ID J:91728]

Kerepesi LA; Hess JA; Nolan TJ; Schad GA; Abraham D. 2006. Complement component C3 is required for protective innate and adaptive immunity to larval strongyloides stercoralis in mice. J Immunol 176(7):4315-22. [PubMed: 16547268]  [MGI Ref ID J:129872]

Kwan WH; Hashimoto D; Paz-Artal E; Ostrow K; Greter M; Raedler H; Medof ME; Merad M; Heeger PS. 2012. Antigen-presenting cell-derived complement modulates graft-versus-host disease. J Clin Invest 122(6):2234-8. [PubMed: 22585573]  [MGI Ref ID J:190492]

Lajoie S; Lewkowich IP; Suzuki Y; Clark JR; Sproles AA; Dienger K; Budelsky AL; Wills-Karp M. 2010. Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nat Immunol 11(10):928-35. [PubMed: 20802484]  [MGI Ref ID J:164688]

Li K; Anderson KJ; Peng Q; Noble A; Lu B; Kelly AP; Wang N; Sacks SH; Zhou W. 2008. Cyclic AMP plays a critical role in C3a-receptor-mediated regulation of dendritic cells in antigen uptake and T-cell stimulation. Blood 112(13):5084-94. [PubMed: 18812470]  [MGI Ref ID J:144259]

Liu J; Lin F; Strainic MG; An F; Miller RH; Altuntas CZ; Heeger PS; Tuohy VK; Medof ME. 2008. IFN-{gamma} and IL-17 Production in Experimental Autoimmune Encephalomyelitis Depends on Local APC-T Cell Complement Production. J Immunol 180(9):5882-9. [PubMed: 18424707]  [MGI Ref ID J:134318]

Nozaki M; Raisler BJ; Sakurai E; Sarma JV; Barnum SR; Lambris JD; Chen Y; Zhang K; Ambati BK; Baffi JZ; Ambati J. 2006. Drusen complement components C3a and C5a promote choroidal neovascularization. Proc Natl Acad Sci U S A 103(7):2328-33. [PubMed: 16452172]  [MGI Ref ID J:106063]

Peng Q; Li K; Anderson K; Farrar CA; Lu B; Smith RA; Sacks SH; Zhou W. 2008. Local production and activation of complement up-regulates the allostimulatory function of dendritic cells through C3a-C3aR interaction. Blood 111(4):2452-61. [PubMed: 18056835]  [MGI Ref ID J:131316]

Qing X; Koo GC; Salmon JE. 2012. Complement regulates conventional DC-mediated NK-cell activation by inducing TGF-beta1 in Gr-1+ myeloid cells. Eur J Immunol 42(7):1723-34. [PubMed: 22535677]  [MGI Ref ID J:187776]

Redecha P; Tilley R; Tencati M; Salmon JE; Kirchhofer D; Mackman N; Girardi G. 2007. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. Blood 110(7):2423-31. [PubMed: 17536017]  [MGI Ref ID J:147022]

Sakuma M; Morooka T; Wang Y; Shi C; Croce K; Gao H; Strainic M; Medof ME; Simon DI. 2010. The intrinsic complement regulator decay-accelerating factor modulates the biological response to vascular injury. Arterioscler Thromb Vasc Biol 30(6):1196-202. [PubMed: 20299685]  [MGI Ref ID J:180868]

Strainic MG; Liu J; Huang D; An F; Lalli PN; Muqim N; Shapiro VS; Dubyak GR; Heeger PS; Medof ME. 2008. Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. Immunity 28(3):425-35. [PubMed: 18328742]  [MGI Ref ID J:132942]

Strainic MG; Shevach EM; An F; Lin F; Medof ME. 2012. Absence of signaling into CD4(+) cells via C3aR and C5aR enables autoinductive TGF-beta1 signaling and induction of Foxp3(+) regulatory T cells. Nat Immunol 14(2):162-71. [PubMed: 23263555]  [MGI Ref ID J:192613]

Tu Z; Bu H; Dennis JE; Lin F. 2010. Efficient osteoclast differentiation requires local complement activation. Blood 116(22):4456-63. [PubMed: 20709903]  [MGI Ref ID J:166640]

Veninga H; Hoek RM; de Vos AF; de Bruin AM; An FQ; van der Poll T; van Lier RA; Medof ME; Hamann J. 2011. A novel role for CD55 in granulocyte homeostasis and anti-bacterial host defense. PLoS One 6(10):e24431. [PubMed: 21984892]  [MGI Ref ID J:178122]

Verschoor A; Neuenhahn M; Navarini AA; Graef P; Plaumann A; Seidlmeier A; Nieswandt B; Massberg S; Zinkernagel RM; Hengartner H; Busch DH. 2011. A platelet-mediated system for shuttling blood-borne bacteria to CD8alpha+ dendritic cells depends on glycoprotein GPIb and complement C3. Nat Immunol 12(12):1194-201. [PubMed: 22037602]  [MGI Ref ID J:179014]

Vieyra M; Leisman S; Raedler H; Kwan WH; Yang M; Strainic MG; Medof ME; Heeger PS. 2011. Complement regulates CD4 T-cell help to CD8 T cells required for murine allograft rejection. Am J Pathol 179(2):766-74. [PubMed: 21704012]  [MGI Ref ID J:174402]

Wysoczynski M; Reca R; Lee H; Wu W; Ratajczak J; Ratajczak MZ. 2009. Defective engraftment of C3aR-/- hematopoietic stem progenitor cells shows a novel role of the C3a-C3aR axis in bone marrow homing. Leukemia 23(8):1455-61. [PubMed: 19357704]  [MGI Ref ID J:151730]

Zhang X; Lewkowich IP; Kohl G; Clark JR; Wills-Karp M; Kohl J. 2009. A protective role for C5a in the development of allergic asthma associated with altered levels of B7-H1 and B7-DC on plasmacytoid dendritic cells. J Immunol 182(8):5123-30. [PubMed: 19342693]  [MGI Ref ID J:147487]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	Upon arrival, mutant mice were bred together to create homozygotes. To maintain the live colony, homozygous mice are bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   06-MAY-06
Diet Information	LabDiet® 5K52/5K67

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.

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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.

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Contact information

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phone:	207-288-6470
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