Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S4 via J1 ES cell line Generation N6F15N1F2 (19-DEC-07)   Donating Investigator Michael Carroll,   The Center for Blood Research

Description
Mice homozygous for the C3 (complement component C3) targeted mutation are viable and fertile. Homozygous mutants exhibit an increased susceptibility to lethal infection by Group B streptococci. Reductions in peritoneal mast cell degranulation, production of tumor necrosis factor alpha, neutrophil infiltration and bacterial clearance have also been reported in these mice. Homozygotes also demonstrate a profound defect in antibody response to T cell dependent antigens. They show a diminished level of peanut agglutin+ germinal centers and a failure in isotype switching despite normal B cell signalling in vitro.

Development
The C3 gene is disrupted by PGK/Neo cassette. Approximately 600 nt of the gene are deleted. A portion of these nts (nt 1850-2214; AA 620-741, pro-C3 numbering) fall within the coding region. The targeting construct was transfected into J1 ES cells. Successful transfectants were injected into 3.5 day old C57BL/6 blastocysts which were then implanted into the uterus of pseudopregnant females. Male chimeric mice were bred with C57BL/6 females.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of C3

000833	B6.SJL-C3c/J
000944	B6.SJL-H2b C3c/2CyJ
000966	B6.SJL-H2s C3c/1CyJ

View Strains carrying other alleles of C3     (3 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

C3^tm1Crr/C3^tm1Crr

        B6.129S4-C3^tm1Crr

• immune system phenotype
• abnormal inflammatory response (MGI Ref ID J:113463)
  • following exposure to LPS then challenge with TNF at the same site to initiate a local Shwartman response, mice fail to exhibit hemorrhage and exhibit reduced fibrin deposition compared to the thrombohemorrhagic vasculitis observed in wild-type mice despite normal neutrophil accumulation
• abnormal neutrophil morphology (MGI Ref ID J:113463)
  • neutrophils that accumulate at the site of a local Shwartman response are round instead of flattened as in wild-type mice
• homeostasis/metabolism phenotype
• abnormal blood chemistry (MGI Ref ID J:113463)
  • mouse serum fails to support neutrophil adhesion unlike serum from wild-type mice
• hematopoietic system phenotype
• abnormal neutrophil morphology (MGI Ref ID J:113463)
  • neutrophils that accumulate at the site of a local Shwartman response are round instead of flattened as in wild-type mice

C3^tm1Crr/C3^tm1Crr

        B6.129S4-C3^tm1Crr/J

• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:136745)
  • mice infected with 500 CFU of S. aureus, show higher numbers of bacterial SFU (intraocular growth) at 24 and 48 hours post-infection, levels are indistinguishable from infected wild-type by 72 hours
• vision/eye phenotype
• *normal* vision/eye phenotype (MGI Ref ID J:136745)
  • eyes infected with 500 CFU S. aureus show mild signs of inflammation at 24 and 48 hours but appear normal at 72 hours
• abnormal eye electrophysiology (MGI Ref ID J:136745)
  • 24 hours after infection with 500 CFU of S. aureus, mice show a transient loss of b-wave amplitude; this stabilizes at a level of 66% of baseline values, similar to what is seen in eyes of infected wild-type mice

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

C3^tm1Crr/C3^tm1Crr

        involves: 129S4/SvJae * C57BL/6

• life span-post-weaning/aging
• abnormal induced morbidity/mortality (MGI Ref ID J:44240)
  • caecal ligation and puncture (CLP) causes greater mortality in mutants than wild-type in the first 24 hours after CLP (100 vs 20% mortality)
  • reconstitution of mice with ip. injection of purified human C3 (HuC3) reduces mortality from 100% to 40% in the first 24 hours
• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:64282)
  • secondary immune responses are similar in wild type and mutant mice, so helper T cell function is normal secondary immune responses are similar in wild-type and mutant mice, so helper T cell function is normal
  • B cells from deficient mice show normal proliferative effects in response to surface IgM crosslinking
• abnormal immune system morphology (MGI Ref ID J:44240)
• abnormal spleen germinal center morphology (MGI Ref ID J:64282)
• decreased spleen germinal center number (MGI Ref ID J:64282)
  • after immunization, wild-type mice develop germinal centers (GC) in ~half of splenic follicles while ~10% of splenic follicles in C3-deficient mice contain GCs
• decreased spleen germinal center size (MGI Ref ID J:64282)
  • diameter of GCs are less than that observed in wild-type
• decreased mast cell number (MGI Ref ID J:44240)
  • after CLP less peritoneal mast cells can be recovered from Cr3-deficient mice compared to controls
• decreased neutrophil cell number (MGI Ref ID J:44240)
  • 1 hour after CLP, 50% of peritoneal cells are neutrophils and after 3 hours, 90% are neutrophils while in C3-deficient mice, after 1 hour only 1% and 45% after 3 hours are neutrophils
• abnormal immune system physiology (MGI Ref ID J:44240)
• abnormal cell-mediated immunity (MGI Ref ID J:30152)
  • in an in vitro assay, opsonization with serum from C3-deficient mice and 1% immune rabbit serum only resulted in a 0.2 log10 reduction in GBS CFU compared to a 1.0 log10 reduction by normal mouse serum
• abnormal mast cell physiology (MGI Ref ID J:44240)
  • mast cells from mutants 1 or 3 hours after CLP show reduced degranulation compared to wild-type (75% of wild-type cells vs <50% of C3-deficient cells)
  • treatment with HuC3 results in comparable levels of mast cell degranulation to wild-type
• abnormal humoral immune response (MGI Ref ID J:64282)
  • in response to immunization with bacteriophage (phiX174), a T cell dependent antigen, C3-deficient mice mount a weak Ig M response but fail to switch to IgG
  • when immunized with a 10-fold higher amount of bacteriophage, mice show a weak IgG response but response is still 10-fold lower than wild-type
• abnormal tumor necrosis factor level (MGI Ref ID J:44240)
  • levels of Tnfa in peritoneal lavage fluids are reduced in C3-deficient mice compared to controls at 1 hour (158 mg/pl vs 400 mg/pl) and 3 hours (218 mg/pl vs 663 pg/ml) after CLP
  • treatment with HuC3 restores levels of Tnfa production in mutants to wild-type levels
• increased susceptibility to bacterial infection (MGI Ref ID J:30152)
  • mice challenged with group B Streptococci (GBS) infection become bacteremic within 3 days and die or clear bacteria and survive; C3-deficient mice challenged with GBS infection showed a decreased LD₅₀ dose compared to immunocompetent controls (LD₅₀ dose: control 6.3 x 10⁴ vs. 1.3 x 10³ in C3-deficient mice)
  • increased mortality from GBS infection compared to controls is limited to the first 3 days after challenge
  • when pregnant dams are immunized with immune rabbit serum, pups are not protected against lethal challenge on day 2 of life (15/20 pups die within 48 hours)
  • at 1 or 3 hours after CLP, cytocentrifuge preparations or peritoneal fluid from C3-deficient mice have reduced neutrophil counts and large numbers of bacteria, compared to wild-type which have few or no bacteria
  • treatment with HuC3 restore neutrophil numbers and enhance bacterial clearance to wild-type levels
• liver inflammation (MGI Ref ID J:30152)
  • mild hepatitis is observed in a small number (1/11) of mice surviving systemic challenge with GBS doses of 10² to 10⁵ CFU upon necropsy 15 days post-challenge; there are aggregates of mononuclear or polymorphonuclear leukocytes in hepatic sinusoids; wild-type animals that receive higher doses of GBS showed similar lesions
• cardiovascular system phenotype
• decreased vascular permeability (MGI Ref ID J:78613)
  • upeon reperfusion of ischemic intestine (jejunum), permeability index (PI) of injured C3-deficient mice is reduced compared to control treated wild-type (PI of 2.25 vs 3.26 in controls)
• digestive/alimentary phenotype
• abnormal intestine morphology (MGI Ref ID J:78613)
  • mice show less evidence of infarction compared to controls
• homeostasis/metabolism phenotype
• abnormal tumor necrosis factor level (MGI Ref ID J:44240)
  • levels of Tnfa in peritoneal lavage fluids are reduced in C3-deficient mice compared to controls at 1 hour (158 mg/pl vs 400 mg/pl) and 3 hours (218 mg/pl vs 663 pg/ml) after CLP
  • treatment with HuC3 restores levels of Tnfa production in mutants to wild-type levels
• decreased susceptibility to injury (MGI Ref ID J:120567)
  • mice are resistant to ischemia reperfusion-induced renal injury
  • serum urea nitrogen is reduced 31% to 55% compared to wild-type mice subjected to ischemia reperfusion
  • neutrophil infiltration at the site of injury was reduced
• hematopoietic system phenotype
• abnormal spleen germinal center morphology (MGI Ref ID J:64282)
• decreased spleen germinal center number (MGI Ref ID J:64282)
  • after immunization, wild-type mice develop germinal centers (GC) in ~half of splenic follicles while ~10% of splenic follicles in C3-deficient mice contain GCs
• decreased spleen germinal center size (MGI Ref ID J:64282)
  • diameter of GCs are less than that observed in wild-type
• decreased mast cell number (MGI Ref ID J:44240)
  • after CLP less peritoneal mast cells can be recovered from Cr3-deficient mice compared to controls
• decreased neutrophil cell number (MGI Ref ID J:44240)
  • 1 hour after CLP, 50% of peritoneal cells are neutrophils and after 3 hours, 90% are neutrophils while in C3-deficient mice, after 1 hour only 1% and 45% after 3 hours are neutrophils
• liver/biliary system phenotype
• liver inflammation (MGI Ref ID J:30152)
  • mild hepatitis is observed in a small number (1/11) of mice surviving systemic challenge with GBS doses of 10² to 10⁵ CFU upon necropsy 15 days post-challenge; there are aggregates of mononuclear or polymorphonuclear leukocytes in hepatic sinusoids; wild-type animals that receive higher doses of GBS showed similar lesions

C3^tm1Crr/C3^tm1Crr

        involves: 129S4/SvJae

• homeostasis/metabolism phenotype
• decreased susceptibility to injury (MGI Ref ID J:128218)
  • following exposure to ethanol, mice do not develop microvesicular or macrovesicular steatosis of the liver and do not accumulate excessive trglycerides as in wild-type mice
  • following exposure to ethanol, mice exhibit a reduced increased in alanine aminotransferase compared to in similarly treated wild-type mice
• liver/biliary system phenotype
• increased resistance to hepatic steatosis (MGI Ref ID J:128218)
  • following exposure to ethanol, mice do not develop microvesicular or macrovesicular steatosis of the liver as in wild-type mice

View Research Applications

Research Applications

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

C3^tm1Crr related

Developmental Biology Research
Lymphoid Tissue Defects (hematopoietic defects)

Immunology and Inflammation Research
Immunodeficiency (specific complement deficiency)
Immunodeficiency Associated with Other Defects
Inflammation

Research Tools
Immunology and Inflammation Research (specific complement deficiency)

Genes & Alleles

Gene & Allele Information

Allele Symbol		C3tm1Crr
Allele Name		targeted mutation 1, Michael C Carroll
Allele Type		Targeted (knock-out)
Common Name(s)		C3-; C3tm1Crr;
Mutation Made By		Michael Carroll,   The Center for Blood Research
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		C3, complement component 3
Chromosome		17
Gene Common Name(s)		AI255234; ARMD9; ASP; CPAMD1; Plp; acylation stimulating protein; complement factor 3; expressed sequence AI255234;
Molecular Note		Insertion of a PGK-neomycin resistance cassette into an exon of the C3 gene deleted sequences that code for the C-terminal region of the beta chain and the N-terminal region of the alpha chain, including the site for processing the pro-C3 molecule. ELISAtesting did not detect C3 protein in serum of homozygous mutant mice. A C3 hemolytic assay did not detect functional C3 activity. [MGI Ref ID J:30152]

Genotyping

Genotyping Information

Genotyping Protocols

C3^tm1Crr, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Hong F; Hansen RD; Yan J; Allendorf DJ; Baran JT; Ostroff GR; Ross GD. 2003. Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells. Cancer Res 63(24):9023-31. [PubMed: 14695221]  [MGI Ref ID J:87069]

Tuzun E; Scott BG; Goluszko E; Higgs S; Christadoss P. 2003. Genetic evidence for involvement of classical complement pathway in induction of experimental autoimmune myasthenia gravis. J Immunol 171(7):3847-54. [PubMed: 14500686]  [MGI Ref ID J:85645]

Yamada K; Miwa T; Liu J; Nangaku M; Song WC. 2004. Critical protection from renal ischemia reperfusion injury by CD55 and CD59. J Immunol 172(6):3869-75. [PubMed: 15004194]  [MGI Ref ID J:88632]

C3^tm1Crr related

Anderson DR; Tsutsui JM; Xie F; Radio SJ; Porter TR. 2007. The role of complement in the adherence of microbubbles to dysfunctional arterial endothelium and atherosclerotic plaque. Cardiovasc Res 73(3):597-606. [PubMed: 17196951]  [MGI Ref ID J:119533]

Atkinson C; Zhu H; Qiao F; Varela JC; Yu J; Song H; Kindy MS; Tomlinson S. 2006. Complement-dependent P-selectin expression and injury following ischemic stroke. J Immunol 177(10):7266-74. [PubMed: 17082645]  [MGI Ref ID J:140616]

Baudino L; Nimmerjahn F; Azeredo da Silveira S; Martinez-Soria E; Saito T; Carroll M; Ravetch JV; Verbeek JS; Izui S. 2008. Differential contribution of three activating IgG Fc receptors (FcgammaRI, FcgammaRIII, and FcgammaRIV) to IgG2a- and IgG2b-induced autoimmune hemolytic anemia in mice. J Immunol 180(3):1948-53. [PubMed: 18209093]  [MGI Ref ID J:131620]

Baumann U; Chouchakova N; Gewecke B; Kohl J; Carroll MC; Schmidt RE; Gessner JE. 2001. Distinct tissue site-specific requirements of mast cells and complement components C3/C5a receptor in IgG immune complex-induced injury of skin and lung. J Immunol 167(2):1022-7. [PubMed: 11441111]  [MGI Ref ID J:120524]

Bergtold A; Desai DD; Gavhane A; Clynes R. 2005. Cell surface recycling of internalized antigen permits dendritic cell priming of B cells. Immunity 23(5):503-14. [PubMed: 16286018]  [MGI Ref ID J:113283]

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]

Buono C; Come CE; Witztum JL; Maguire GF; Connelly PW; Carroll M; Lichtman AH. 2002. Influence of C3 deficiency on atherosclerosis. Circulation 105(25):3025-31. [PubMed: 12081998]  [MGI Ref ID J:103349]

Burrer R; Buchmeier MJ; Wolfe T; Ting JP; Feuer R; Iglesias A; von Herrath MG. 2007. Exacerbated pathology of viral encephalitis in mice with central nervous system-specific autoantibodies. Am J Pathol 170(2):557-66. [PubMed: 17255324]  [MGI Ref ID J:117906]

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]

Coles B; Lewis R; Anning PB; Morton J; Baalasubramanian S; Morgan BP; O'Donnell VB. 2007. CD59 or C3 are not requred for angiotensin II-dependent hypertension or hypertrophy in mice. Immunology 121(4):518-25. [PubMed: 17433074]  [MGI Ref ID J:125538]

Cortes-Hernandez J; Fossati-Jimack L; Carugati A; Potter PK; Walport MJ; Cook HT; Botto M. 2002. Murine glomerular mesangial cell uptake of apoptotic cells is inefficient and involves serum-mediated but complement-independent mechanisms. Clin Exp Immunol 130(3):459-66. [PubMed: 12452836]  [MGI Ref ID J:115531]

Cunnion KM; Benjamin DK Jr; Hester CG; Frank MM. 2004. Role of complement receptors 1 and 2 (CD35 and CD21), C3, C4, and C5 in survival by mice of Staphylococcus aureus bacteremia. J Lab Clin Med 143(6):358-65. [PubMed: 15192652]  [MGI Ref ID J:101948]

Einav S; Pozdnyakova OO; Ma M; Carroll MC. 2002. Complement C4 is protective for lupus disease independent of C3. J Immunol 168(3):1036-41. [PubMed: 11801636]  [MGI Ref ID J:127292]

Engelbert M; Gilmore MS. 2005. Fas ligand but not complement is critical for control of experimental Staphylococcus aureus Endophthalmitis. Invest Ophthalmol Vis Sci 46(7):2479-86. [PubMed: 15980239]  [MGI Ref ID J:136745]

Farrar CA; Zhou W; Lin T; Sacks SH. 2006. Local extravascular pool of C3 is a determinant of postischemic acute renal failure. FASEB J 20(2):217-26. [PubMed: 16449793]  [MGI Ref ID J:105786]

Fischer MB; Ma M; Goerg S; Zhou X; Xia J; Finco O; Han S; Kelsoe G; Howard RG; Rothstein TL; Kremmer E; Rosen FS; Carroll MC. 1996. Regulation of the B cell response to T-dependent antigens by classical pathway complement. J Immunol 157(2):549-56. [PubMed: 8752901]  [MGI Ref ID J:64282]

Fischer MB; Prodeus AP; Nicholson-Weller A; Ma M; Murrow J; Reid RR; Warren HB; Lage AL; Moore FD Jr; Rosen FS; Carroll MC. 1997. Increased susceptibility to endotoxin shock in complement C3- and C4-deficient mice is corrected by C1 inhibitor replacement. J Immunol 159(2):976-82. [PubMed: 9218619]  [MGI Ref ID J:78654]

Gaspal FM; McConnell FM; Kim MY; Gray D; Kosco-Vilbois MH; Raykundalia CR; Botto M; Lane PJ. 2006. The generation of thymus-independent germinal centers depends on CD40 but not on CD154, the T cell-derived CD40-ligand. Eur J Immunol 36(7):1665-73. [PubMed: 16783845]  [MGI Ref ID J:115798]

Giacomin PR; Gordon DL; Botto M; Daha MR; Sanderson SD; Taylor SM; Dent LA. 2008. The role of complement in innate, adaptive and eosinophil-dependent immunity to the nematode Nippostrongylus brasiliensis. Mol Immunol 45(2):446-55. [PubMed: 17675237]  [MGI Ref ID J:125347]

Green RS; Stone EL; Tenno M; Lehtonen E; Farquhar MG; Marth JD. 2007. Mammalian N-Glycan Branching Protects against Innate Immune Self-Recognition and Inflammation in Autoimmune Disease Pathogenesis. Immunity 27(2):308-20. [PubMed: 17681821]  [MGI Ref ID J:124348]

Hall LR; Diaconu E; Pearlman E. 2001. A dominant role for Fc gamma receptors in antibody-dependent corneal inflammation. J Immunol 167(2):919-25. [PubMed: 11441099]  [MGI Ref ID J:120230]

Harbers SO; Crocker A; Catalano G; D'Agati V; Jung S; Desai DD; Clynes R. 2007. Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance. J Clin Invest 117(5):1361-9. [PubMed: 17446931]  [MGI Ref ID J:122114]

Hasegawa M; Fujimoto M; Poe JC; Steeber DA; Tedder TF. 2001. CD19 can regulate B lymphocyte signal transduction independent of complement activation. J Immunol 167(6):3190-200. [PubMed: 11544305]  [MGI Ref ID J:118767]

Hebert MJ; Takano T; Papayianni A; Rennke HG; Minto A; Salant DJ; Carroll MC; Brady HR. 1998. Acute nephrotoxic serum nephritis in complement knockout mice: relative roles of the classical and alternate pathways in neutrophil recruitment and proteinuria. Nephrol Dial Transplant 13(11):2799-803. [PubMed: 9829481]  [MGI Ref ID J:77011]

Hirahashi J; Mekala D; Van Ziffle J; Xiao L; Saffaripour S; Wagner DD; Shapiro SD; Lowell C; Mayadas TN. 2006. Mac-1 signaling via Src-family and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy. Immunity 25(2):271-83. [PubMed: 16872848]  [MGI Ref ID J:113463]

Hod EA; Cadwell CM; Liepkalns JS; Zimring JC; Sokol SA; Schirmer DA; Jhang J; Spitalnik SL. 2008. Cytokine storm in a mouse model of IgG-mediated hemolytic transfusion reactions. Blood 112(3):891-4. [PubMed: 18483395]  [MGI Ref ID J:138442]

Hoffmeister KM; Felbinger TW; Falet H; Denis CV; Bergmeier W; Mayadas TN; von Andrian UH; Wagner DD; Stossel TP; Hartwig JH. 2003. The clearance mechanism of chilled blood platelets. Cell 112(1):87-97. [PubMed: 12526796]  [MGI Ref ID J:107707]

Hong F; Hansen RD; Yan J; Allendorf DJ; Baran JT; Ostroff GR; Ross GD. 2003. Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells. Cancer Res 63(24):9023-31. [PubMed: 14695221]  [MGI Ref ID J:87069]

Imai M; Landen C; Ohta R; Cheung NK; Tomlinson S. 2005. Complement-mediated mechanisms in anti-GD2 monoclonal antibody therapy of murine metastatic cancer. Cancer Res 65(22):10562-8. [PubMed: 16288049]  [MGI Ref ID J:103401]

Ip WK; Takahashi K; Moore KJ; Stuart LM; Ezekowitz RA. 2008. Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome. J Exp Med 205(1):169-81. [PubMed: 18180310]  [MGI Ref ID J:131122]

Kang YS; Do Y; Lee HK; Park SH; Cheong C; Lynch RM; Loeffler JM; Steinman RM; Park CG. 2006. A dominant complement fixation pathway for pneumococcal polysaccharides initiated by SIGN-R1 interacting with C1q. Cell 125(1):47-58. [PubMed: 16615889]  [MGI Ref ID J:115872]

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]

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]

Koch CA; Jordan CE; Platt JL. 2006. Complement-dependent control of teratoma formation by embryonic stem cells. J Immunol 177(7):4803-9. [PubMed: 16982921]  [MGI Ref ID J:139307]

Kopf M; Abel B; Gallimore A; Carroll M; Bachmann MF. 2002. Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection. Nat Med 8(4):373-8. [PubMed: 11927943]  [MGI Ref ID J:126202]

Kopf M; Herren S; Wiles MV; Pepys MB; Kosco-Vilbois MH. 1998. Interleukin 6 influences germinal center development and antibody production via a contribution of C3 complement component. J Exp Med 188(10):1895-906. [PubMed: 9815267]  [MGI Ref ID J:79296]

Kuehn MH; Kim CY; Jiang B; Dumitrescu AV; Kwon YH. 2008. Disruption of the complement cascade delays retinal ganglion cell death following retinal ischemia-reperfusion. Exp Eye Res 87(2):89-95. [PubMed: 18572163]  [MGI Ref ID J:138248]

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]

Liang Y; Li S; Guo Q; Zhang Y; Wen C; Zou Q; Su B. 2007. Complement 3-deficient mice are not protected against MPTP-induced dopaminergic neurotoxicity. Brain Res 1178:132-40. [PubMed: 17900537]  [MGI Ref ID J:127243]

Liu J; Miwa T; Hilliard B; Chen Y; Lambris JD; Wells AD; Song WC. 2005. The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo. J Exp Med 201(4):567-77. [PubMed: 15710649]  [MGI Ref ID J:96689]

Longhi MP; Sivasankar B; Omidvar N; Morgan BP; Gallimore A. 2005. Cutting edge: murine CD59a modulates antiviral CD4+ T cell activity in a complement-independent manner. J Immunol 175(11):7098-102. [PubMed: 16301611]  [MGI Ref ID J:122201]

Lund FE; Schuer K; Hollifield M; Randall TD; Garvy BA. 2003. Clearance of Pneumocystis carinii in mice is dependent on B cells but not on P carinii-specific antibody. J Immunol 171(3):1423-30. [PubMed: 12874234]  [MGI Ref ID J:120666]

Maier M; Peng Y; Jiang L; Seabrook TJ; Carroll MC; Lemere CA. 2008. Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice. J Neurosci 28(25):6333-41. [PubMed: 18562603]  [MGI Ref ID J:135902]

Mocco J; Mack WJ; Ducruet AF; Sosunov SA; Sughrue ME; Hassid BG; Nair MN; Laufer I; Komotar RJ; Claire M; Holland H; Pinsky DJ; Connolly ES Jr. 2006. Complement component C3 mediates inflammatory injury following focal cerebral ischemia. Circ Res 99(2):209-17. [PubMed: 16778128]  [MGI Ref ID J:123658]

Mold C; Rodic-Polic B; Du Clos TW. 2002. Protection from Streptococcus pneumoniae infection by C-reactive protein and natural antibody requires complement but not Fc gamma receptors. J Immunol 168(12):6375-81. [PubMed: 12055255]  [MGI Ref ID J:123793]

Moll T; Nitschke L; Carroll M; Ravetch JV; Izui S. 2004. A critical role for Fc gamma RIIB in the induction of rheumatoid factors. J Immunol 173(7):4724-8. [PubMed: 15383609]  [MGI Ref ID J:93718]

Moller-Kristensen M; Hamblin MR; Thiel S; Jensenius JC; Takahashi K. 2007. Burn injury reveals altered phenotype in mannan-binding lectin-deficient mice. J Invest Dermatol 127(6):1524-31. [PubMed: 17363917]  [MGI Ref ID J:121549]

Morrison TE; Fraser RJ; Smith PN; Mahalingam S; Heise MT. 2007. Complement contributes to inflammatory tissue destruction in a mouse model of ross river virus-induced disease. J Virol 81(10):5132-43. [PubMed: 17314163]  [MGI Ref ID J:121097]

Morton J; Coles B; Wright K; Gallimore A; Morrow JD; Terry ES; Anning PB; Morgan BP; Dioszeghy V; Kuhn H; Chaitidis P; Hobbs AJ; Jones SA; O'Donnell VB. 2008. Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFNgamma-dependent iNOS expression in the vasculature of healthy mice. Blood 111(10):5187-94. [PubMed: 18281503]  [MGI Ref ID J:135580]

Mullaly SC; Kubes P. 2007. Mast cell-expressed complement receptor, not TLR2, is the main detector of zymosan in peritonitis. Eur J Immunol 37(1):224-34. [PubMed: 17154261]  [MGI Ref ID J:117071]

Nimmerjahn F; Anthony RM; Ravetch JV. 2007. Agalactosylated IgG antibodies depend on cellular Fc receptors for in vivo activity. Proc Natl Acad Sci U S A 104(20):8433-7. [PubMed: 17485663]  [MGI Ref ID J:121840]

Nimmerjahn F; Ravetch JV. 2005. Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science 310(5753):1510-2. [PubMed: 16322460]  [MGI Ref ID J:103229]

Ochsenbein AF; Pinschewer DD; Odermatt B; Carroll MC; Hengartner H; Zinkernagel RM. 1999. Protective T cell-independent antiviral antibody responses are dependent on complement. J Exp Med 190(8):1165-74. [PubMed: 10523614]  [MGI Ref ID J:115126]

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]

Peng Q; Li K; Patel H; Sacks SH; Zhou W. 2006. Dendritic cell synthesis of C3 is required for full T cell activation and development of a Th1 phenotype. J Immunol 176(6):3330-41. [PubMed: 16517700]  [MGI Ref ID J:129540]

Pozdnyakova O; Guttormsen HK; Lalani FN; Carroll MC; Kasper DL. 2003. Impaired antibody response to group B streptococcal type III capsular polysaccharide in C3- and complement receptor 2-deficient mice. J Immunol 170(1):84-90. [PubMed: 12496386]  [MGI Ref ID J:127041]

Pritchard MT; McMullen MR; Stavitsky AB; Cohen JI; Lin F; Medof ME; Nagy LE. 2007. Differential contributions of C3, C5, and decay-accelerating factor to ethanol-induced fatty liver in mice. Gastroenterology 132(3):1117-26. [PubMed: 17383432]  [MGI Ref ID J:128218]

Prodeus AP; Zhou X; Maurer M; Galli SJ; Carroll MC. 1997. Impaired mast cell-dependent natural immunity in complement C3-deficient mice. Nature 390(6656):172-5. [PubMed: 9367154]  [MGI Ref ID J:44240]

Qiao F; Atkinson C; Song H; Pannu R; Singh I; Tomlinson S. 2006. Complement plays an important role in spinal cord injury and represents a therapeutic target for improving recovery following trauma. Am J Pathol 169(3):1039-47. [PubMed: 16936276]  [MGI Ref ID J:112353]

Qin D; Wu J; Carroll MC; Burton GF; Szakal AK; Tew JG. 1998. Evidence for an important interaction between a complement-derived CD21 ligand on follicular dendritic cells and CD21 on B cells in the initiation of IgG responses. J Immunol 161(9):4549-54. [PubMed: 9794381]  [MGI Ref ID J:112151]

Qin X; Dobarro M; Bedford SJ; Ferris S; Miranda PV; Song W; Bronson RT; Visconti PE; Halperin JA. 2005. Further characterization of reproductive abnormalities in mCd59b knockout mice: a potential new function of mCd59 in male reproduction. J Immunol 175(10):6294-302. [PubMed: 16272280]  [MGI Ref ID J:108100]

Quigg RJ; Lim A; Haas M; Alexander JJ; He C; Carroll MC. 1998. Immune complex glomerulonephritis in C4- and C3-deficient mice. Kidney Int 53(2):320-30. [PubMed: 9461092]  [MGI Ref ID J:47055]

Ratajczak J; Reca R; Kucia M; Majka M; Allendorf DJ; Baran JT; Janowska-Wieczorek A; Wetsel RA; Ross GD; Ratajczak MZ. 2004. Mobilization studies in mice deficient in either C3 or C3a receptor (C3aR) reveal a novel role for complement in retention of hematopoietic stem/progenitor cells in bone marrow. Blood 103(6):2071-8. [PubMed: 14604969]  [MGI Ref ID J:88568]

Rozanov DV; Savinov AY; Golubkov VS; Tomlinson S; Strongin AY. 2006. Interference with the complement system by tumor cell membrane type-1 matrix metalloproteinase plays a significant role in promoting metastasis in mice. Cancer Res 66(12):6258-63. [PubMed: 16778201]  [MGI Ref ID J:110103]

Sheerin NS; Risley P; Abe K; Tang Z; Wong W; Lin T; Sacks SH. 2008. Synthesis of complement protein C3 in the kidney is an important mediator of local tissue injury. FASEB J 22(4):1065-72. [PubMed: 18039928]  [MGI Ref ID J:135262]

Sheerin NS; Springall T; Carroll M; Sacks SH. 1999. Altered distribution of intraglomerular immune complexes in C3-deficient mice. Immunology 97(3):393-9. [PubMed: 10447759]  [MGI Ref ID J:56335]

Sheerin NS; Springall T; Carroll MC; Hartley B; Sacks SH. 1997. Protection against anti-glomerular basement membrane (GBM)-mediated nephritis in C3- and C4-deficient mice. Clin Exp Immunol 110(3):403-9. [PubMed: 9409643]  [MGI Ref ID J:44715]

Sood R; Sholl L; Isermann B; Zogg M; Coughlin SR; Weiler H. 2008. Maternal Par4 and platelets contribute to defective placenta formation in mouse embryos lacking thrombomodulin. Blood 112(3):585-91. [PubMed: 18490515]  [MGI Ref ID J:138440]

Springall T; Sheerin NS; Abe K; Holers VM; Wan H; Sacks SH. 2001. Epithelial secretion of C3 promotes colonization of the upper urinary tract by Escherichia coli. Nat Med 7(7):801-6. [PubMed: 11433344]  [MGI Ref ID J:70251]

Stevens B; Allen NJ; Vazquez LE; Howell GR; Christopherson KS; Nouri N; Micheva KD; Mehalow AK; Huberman AD; Stafford B; Sher A; Litke AM; Lambris JD; Smith SJ; John SW; Barres BA. 2007. The classical complement cascade mediates CNS synapse elimination. Cell 131(6):1164-78. [PubMed: 18083105]  [MGI Ref ID J:137589]

Stokol T; O'Donnell P; Xiao L; Knight S; Stavrakis G; Botto M; von Andrian UH; Mayadas TN. 2004. C1q governs deposition of circulating immune complexes and leukocyte Fcgamma receptors mediate subsequent neutrophil recruitment. J Exp Med 200(7):835-46. [PubMed: 15466618]  [MGI Ref ID J:93949]

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]

Sun K; Metzger DW. 2008. Inhibition of pulmonary antibacterial defense by interferon-gamma during recovery from influenza infection. Nat Med 14(5):558-64. [PubMed: 18438414]  [MGI Ref ID J:136669]

Sylvestre D; Clynes R; Ma M; Warren H; Carroll MC; Ravetch JV. 1996. Immunoglobulin G-mediated inflammatory responses develop normally in complement-deficient mice. J Exp Med 184(6):2385-92. [PubMed: 8976192]  [MGI Ref ID J:78296]

Takahashi K; Shi L; Gowda LD; Ezekowitz RA. 2005. Relative roles of complement factor 3 and mannose-binding lectin in host defense against infection. Infect Immun 73(12):8188-93. [PubMed: 16299314]  [MGI Ref ID J:104305]

Tang T; Rosenkranz A; Assmann KJM; Goodman MJ; Gutierrez-Ramos JC ; Carroll MC ; Cotran RS ; Mayadas TN. 1997. A role for Mac-1 (CDIIb/CD18) in immune complex-stimulated neutrophil function in vivo: Mac-1 deficiency abrogates sustained Fcgamma receptor-dependent neutrophil adhesion and complement-dependent proteinuria in acute glomerulonephritis. J Exp Med 186(11):1853-63. [PubMed: 9382884]  [MGI Ref ID J:44403]

Taylor PR; Carugati A; Fadok VA; Cook HT; Andrews M; Carroll MC; Savill JS; Henson PM; Botto M; Walport MJ. 2000. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 192(3):359-66. [PubMed: 10934224]  [MGI Ref ID J:63875]

Trcka J; Moroi Y; Clynes RA; Goldberg SM; Bergtold A; Perales MA; Ma M; Ferrone CR; Carroll MC; Ravetch JV; Houghton AN. 2002. Redundant and alternative roles for activating Fc receptors and complement in an antibody-dependent model of autoimmune vitiligo. Immunity 16(6):861-8. [PubMed: 12121667]  [MGI Ref ID J:113538]

Trendelenburg M; Fossati-Jimack L; Cortes-Hernandez J; Turnberg D; Lewis M; Izui S; Cook HT; Botto M. 2005. The role of complement in cryoglobulin-induced immune complex glomerulonephritis. J Immunol 175(10):6909-14. [PubMed: 16272350]  [MGI Ref ID J:119691]

Turnberg D; Lewis M; Moss J; Xu Y; Botto M; Cook HT. 2006. Complement activation contributes to both glomerular and tubulointerstitial damage in adriamycin nephropathy in mice. J Immunol 177(6):4094-102. [PubMed: 16951374]  [MGI Ref ID J:138043]

Tuzun E; Scott BG; Goluszko E; Higgs S; Christadoss P. 2003. Genetic evidence for involvement of classical complement pathway in induction of experimental autoimmune myasthenia gravis. J Immunol 171(7):3847-54. [PubMed: 14500686]  [MGI Ref ID J:85645]

Twohig J; Kulik L; Haluszczak C; Reuter J; Rossbach A; Bull M; Holers VM; Marchbank KJ. 2007. Defective B cell ontogeny and immune response in human complement receptor 2 (CR2, CD21) transgenic mice is partially recovered in the absence of C3. Mol Immunol 44(13):3434-44. [PubMed: 17379312]  [MGI Ref ID J:123562]

Verschoor A; Brockman MA; Gadjeva M; Knipe DM; Carroll MC. 2003. Myeloid C3 determines induction of humoral responses to peripheral herpes simplex virus infection. J Immunol 171(10):5363-71. [PubMed: 14607939]  [MGI Ref ID J:119310]

Welch TR; Blystone LW. 2005. C3 is central to the interstitial component of experimental immune complex glomerulonephritis. Clin Immunol 115(1):80-4. [PubMed: 15870025]  [MGI Ref ID J:105037]

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Wysoczynski M; Kucia M; Ratajczak J; Ratajczak MZ. 2007. Cleavage fragments of the third complement component (C3) enhance stromal derived factor-1 (SDF-1)-mediated platelet production during reactive postbleeding thrombocytosis. Leukemia 21(5):973-82. [PubMed: 17330096]  [MGI Ref ID J:121386]

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Yuste J; Botto M; Paton JC; Holden DW; Brown JS. 2005. Additive inhibition of complement deposition by pneumolysin and PspA facilitates Streptococcus pneumoniae septicemia. J Immunol 175(3):1813-9. [PubMed: 16034123]  [MGI Ref ID J:107276]

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de Jong JM; Schuurhuis DH; Ioan-Facsinay A; van der Voort EI; Huizinga TW; Ossendorp F; Toes RE; Verbeek JS. 2006. Murine Fc receptors for IgG are redundant in facilitating presentation of immune complex derived antigen to CD8(+) T cells in vivo. Mol Immunol 43(13):2045-50. [PubMed: 16513171]  [MGI Ref ID J:108110]

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Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-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

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
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

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

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

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.