Strain Name:

C.129S4(B6)-C5ar1tm1Cge/J

Stock Number:

006845

Availability:

Repository- Live

Use Restrictions Apply, see Purchasing Information

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Mating SystemHomozygote x Homozygote         (Female x Male)
Specieslaboratory mouse
Generation?N10N1F0 (05-DEC-07)
 
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 gross physical or behavioral abnormalities when maintained under barrier conditions. No mRNA is detected by Northern blot analysis of bone marrow cells isolated from homozygotes, and neutrophils fail to respond to recombinant C5a in vitro. The immune response of homozygous mice following inoculation or challenge has been characterized on a C57BL/6 background in a number of studies. Following intratracheal inoculation, mutant mice have impaired bacterial clearance in the lungs, associated with extensive secondary infection, despite increased neutrophil accumulation. Conversely, homozygous mutants are protected against immune-complex-associated injury in the lung, peritoneum, skin, and kidney but not against experimental autoimmune encephalomyelitis. Induced acute pancreatitis and pancreatitis-associated lung injury is more severe in homozygotes compared to wildtype. On a BALB/c background, homozygous mutant mice are more resistant to dermal infection, and lymph node cells have greatly increased antigen recall, as measured by interferon gamma secretion, compared to wild type. Homozygotes fail to develop airway hyper-reactivity in hapten asthma models (background not-identified). This mutant can be used to study many lung-associated diseases, immune complex associated injury, and complement-mediated innate immunity.

Development
A targeting vector containing a mouse phosphoglycerate kinase promoter-driven neomycin resistance gene was used to replace the entire coding region of the endogenous gene. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells, and correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were crossed to C57BL/6 females. Heterozygotes were mated to C57BL/6 mice for 2 generations and then backcrossed 10 generations to BALB/c before being made homozygous. Upon arrival at The Jackson Laboratory, homozygous mice were bred at least one generation to BALB/cJ (Stock No. 000651).

Control Information

  Control
   000651 BALB/cJ
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   C5ar1tm1Cge allele
005676   STOCK C5ar1tm1Cge/J
View Strains carrying   C5ar1tm1Cge     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

Mammalian Phenotype Terms assigned by genotype

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

C5ar1tm1Cge/C5ar1tm1Cge

        involves: 129S4/SvJae
  • immune system phenotype
  • abnormal humoral immune response (MGI Ref ID J:35529)
    • after injection of chicken egg albumin in the tail and administration of antibodies to egg albumin intratracheally, the null mice exhibit almost complete protection from inflammatory response upon examination of lung tissue
  • increased susceptibility to bacterial infection (MGI Ref ID J:69177)
    • increased sensitivity to infection by Pseudomonas aeruginosa, death by second day after innoculation

Research Applications

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

Immunology and Inflammation Research
Autoimmunity (specific complement deficiency)

Research Tools
Immunology and Inflammation Research (genes regulating susceptibility to infectious disease and endotoxin)
Immunology and Inflammation Research (specific complement deficiency)

C5ar1tm1Cge related

Immunology and Inflammation Research
Autoimmunity (specific complement deficiency)

Research Tools
Immunology and Inflammation Research (genes regulating susceptibility to infectious disease and endotoxin)
Immunology and Inflammation Research (specific complement deficiency)

Genes & Alleles

Gene & Allele Information

Allele Symbol C5ar1tm1Cge
Allele Name targeted mutation 1, Craig Gerard
Common Name(s) C5aR-; C5aRKO;
Mutation Made By Craig Gerard,   Childrens' Hospital Boston, Harvard MS
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name C5ar1, complement component 5a receptor 1
Chromosome 7
Gene Common Name(s) C5A; C5AR; C5R1; C5r1; CD88; D7Msu1; DNA segment, Chr 7, Michigan State University 1; complement component 5, receptor 1;
Molecular Note A PGK-neomycin resistance cassette replaced the entire coding region of the gene. Northern analysis of bone marrow cells did not detect expression in homozygous mutant mice. [MGI Ref ID J:69177]

Genotyping

Genotyping Information

Genotyping Protocols

C5ar1tm1Cge, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Hopken UE; Lu B; Gerard NP; Gerard C. 1996. The C5a chemoattractant receptor mediates mucosal defence to infection. Nature 383(6595):86-9. [PubMed: 8779720]  [MGI Ref ID J:69177]

Additional References

C5ar1tm1Cge 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]

Bhatia M; Saluja AK; Singh VP; Frossard JL; Lee HS; Bhagat L; Gerard C; Steer ML. 2001. Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury. Am J Physiol Gastrointest Liver Physiol 280(5):G974-8. [PubMed: 11292607]  [MGI Ref ID J:69304]

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]

Bozic CR; Lu B; Hopken UE; Gerard C; Gerard NP. 1996. Neurogenic amplification of immune complex inflammation. Science 273(5282):1722-5. [PubMed: 8781237]  [MGI Ref ID J:35529]

Clynes R; Maizes JS; Guinamard R; Ono M; Takai T; Ravetch JV. 1999. Modulation of immune complex-induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc receptors. J Exp Med 189(1):179-85. [PubMed: 9874574]  [MGI Ref ID J:112378]

Fan G; Jiang YP; Lu Z; Martin DW; Kelly DJ; Zuckerman JM; Ballou LM; Cohen IS; Lin RZ. 2005. A transgenic mouse model of heart failure using inducible Galpha q. J Biol Chem 280(48):40337-46. [PubMed: 16210321]  [MGI Ref ID J:104100]

Godau J; Heller T; Hawlisch H; Trappe M; Howells E; Best J; Zwirner J; Verbeek JS; Hogarth PM; Gerard C; Van Rooijen N; Klos A; Gessner JE; Kohl J. 2004. C5a initiates the inflammatory cascade in immune complex peritonitis. J Immunol 173(5):3437-45. [PubMed: 15322209]  [MGI Ref ID J:92709]

Hawlisch H; Belkaid Y; Baelder R; Hildeman D; Gerard C; Kohl J. 2005. C5a negatively regulates toll-like receptor 4-induced immune responses. Immunity 22(4):415-26. [PubMed: 15845447]  [MGI Ref ID J:97987]

Hopken UE; Lu B; Gerard NP; Gerard C. 1997. Impaired inflammatory responses in the reverse arthus reaction through genetic deletion of the C5a receptor. J Exp Med 186(5):749-56. [PubMed: 9271590]  [MGI Ref ID J:99834]

Kawikova I; Paliwal V; Szczepanik M; Itakura A; Fukui M; Campos RA; Geba GP; Homer RJ; Iliopoulou BP; Pober JS; Tsuji RF; Askenase PW. 2004. Airway hyper-reactivity mediated by B-1 cell immunoglobulin M antibody generating complement C5a at 1 day post-immunization in a murine hapten model of non-atopic asthma. Immunology 113(2):234-45. [PubMed: 15379984]  [MGI Ref ID J:92933]

Kerr AR; Paterson GK; Riboldi-Tunnicliffe A; Mitchell TJ. 2005. Innate immune defense against pneumococcal pneumonia requires pulmonary complement component C3. Infect Immun 73(7):4245-52. [PubMed: 15972516]  [MGI Ref ID J:99281]

Kohl J; Baelder R; Lewkowich IP; Pandey MK; Hawlisch H; Wang L; Best J; Herman NS; Sproles AA; Zwirner J; Whitsett JA; Gerard C; Sfyroera G; Lambris JD; Wills-Karp M. 2006. A regulatory role for the C5a anaphylatoxin in type 2 immunity in asthma. J Clin Invest 116(3):783-96. [PubMed: 16511606]  [MGI Ref ID J:106480]

Kumar V; Ali SR; Konrad S; Zwirner J; Verbeek JS; Schmidt RE; Gessner JE. 2006. Cell-derived anaphylatoxins as key mediators of antibody-dependent type II autoimmunity in mice. J Clin Invest 116(2):512-20. [PubMed: 16453025]  [MGI Ref ID J:105421]

Lalli PN; Strainic MG; Yang M; Lin F; Medof ME; Heeger PS. 2008. Locally produced C5a binds to T cell-expressed C5aR to enhance effector T-cell expansion by limiting antigen-induced apoptosis. Blood 112(5):1759-66. [PubMed: 18567839]  [MGI Ref ID J:138718]

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]

Looney MR; Su X; Van Ziffle JA; Lowell CA; Matthay MA. 2006. Neutrophils and their Fc gamma receptors are essential in a mouse model of transfusion-related acute lung injury. J Clin Invest 116(6):1615-23. [PubMed: 16710475]  [MGI Ref ID J:110368]

Mehlhop E; Diamond MS. 2006. Protective immune responses against West Nile virus are primed by distinct complement activation pathways. J Exp Med 203(5):1371-81. [PubMed: 16651386]  [MGI Ref ID J:124138]

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]

Norman MU; Hulliger S; Colarusso P; Kubes P. 2008. Multichannel fluorescence spinning disk microscopy reveals early endogenous CD4 T cell recruitment in contact sensitivity via complement. J Immunol 180(1):510-21. [PubMed: 18097053]  [MGI Ref ID J:130912]

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]

Okinaga S; Slattery D; Humbles A; Zsengeller Z; Morteau O; Kinrade MB; Brodbeck RM; Krause JE; Choe HR; Gerard NP; Gerard C. 2003. C5L2, a nonsignaling C5A binding protein. Biochemistry 42(31):9406-15. [PubMed: 12899627]  [MGI Ref ID J:115691]

Osaka H; McGinty A; Hoepken UE; Lu B; Gerard C; Pasinetti GM. 1999. Expression of C5a receptor in mouse brain: role in signal transduction and neurodegeneration. Neuroscience 88(4):1073-82. [PubMed: 10336122]  [MGI Ref ID J:52135]

Reiman R; Gerard C; Campbell IL; Barnum SR. 2002. Disruption of the C5a receptor gene fails to protect against experimental allergic encephalomyelitis. Eur J Immunol 32(4):1157-63. [PubMed: 11932923]  [MGI Ref ID J:75976]

Rittirsch D; Flierl MA; Nadeau BA; Day DE; Huber-Lang M; Mackay CR; Zetoune FS; Gerard NP; Cianflone K; Kohl J; Gerard C; Sarma JV; Ward PA. 2008. Functional roles for C5a receptors in sepsis. Nat Med 14(5):551-7. [PubMed: 18454156]  [MGI Ref ID J:136703]

Scholzen TE; Steinhoff M; Sindrilaru A; Schwarz A; Bunnett NW; Luger TA; Armstrong CA; Ansel JC. 2004. Cutaneous allergic contact dermatitis responses are diminished in mice deficient in neurokinin 1 receptors and augmented by neurokinin 2 receptor blockage. FASEB J 18(9):1007-9. [PubMed: 15084523]  [MGI Ref ID J:118457]

Skokowa J; Ali SR; Felda O; Kumar V; Konrad S; Shushakova N; Schmidt RE; Piekorz RP; Nurnberg B; Spicher K; Birnbaumer L; Zwirner J; Claassens JW; Verbeek JS; van Rooijen N; Kohl J; Gessner JE. 2005. Macrophages induce the inflammatory response in the pulmonary Arthus reaction through G alpha i2 activation that controls C5aR and Fc receptor cooperation. J Immunol 174(5):3041-50. [PubMed: 15728518]  [MGI Ref ID J:97718]

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]

Tsuji RF; Kawikova I; Ramabhadran R; Akahira-Azuma M; Taub D; Hugli TE; Gerard C; Askenase PW. 2000. Early local generation of C5a initiates the elicitation of contact sensitivity by leading to early T cell recruitment. J Immunol 165(3):1588-98. [PubMed: 10903768]  [MGI Ref ID J:120437]

Welch TR; Frenzke M; Witte D; Davis AE. 2002. C5a is important in the tubulointerstitial component of experimental immune complex glomerulonephritis. Clin Exp Immunol 130(1):43-8. [PubMed: 12296852]  [MGI Ref ID J:79194]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice may be bred as homozygotes. For homozygous colonies, SPF conditions are recommended as mutant mice have impaired clearance of bacterial infection.
Diet Information LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations             View   International   Pricing
Weeks of AgePrice*GenderGenotypes Provided
Individual Mouse Price $155.70Female or MaleHomozygous for C5ar1tm1Cge
Pairs /Price*Pair Genotype
$311.40Homozygous for C5ar1tm1Cge x Homozygous for C5ar1tm1Cge
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes

Pricing for International shipping destinations             View   USA, Canada and Mexico   Pricing
Weeks of AgePrice*GenderGenotypes Provided
Individual Mouse Price $202.50Female or MaleHomozygous for C5ar1tm1Cge
Pairs /Price*Pair Genotype
$404.90Homozygous for C5ar1tm1Cge x Homozygous for C5ar1tm1Cge
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes

Control Information

  Control
   000651 BALB/cJ
 
  Considerations for Choosing Controls
  USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
  International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

View JAX® Mice & Services Conditions of Use.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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.
Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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