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Phenotypes Associated with This Genotype
Genotype
MGI:2429606
Allelic
Composition
C3tm1Crr/C3tm1Crr
Genetic
Background
involves: 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
C3tm1Crr mutation (4 available); any C3 mutation (10 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

C3tm1Crr/C3tm1Crr exhibit protection from hepatic ischemia reperfusion injury

mortality/aging
• poor survival (20%) after 30 minutes of ischemia while 70% partial hepatectomy performed
• 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
N
• 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
• after CLP less peritoneal mast cells can be recovered from Cr3-deficient mice compared to controls
• 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
• bone marrow cells incubated with 1,25(OH)2 vitamin D3 produce fewer osteoclasts than do cells from controls
• 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
• diameter of GCs are less than that observed in wild-type
• reduced levels at 6 and 24 hours after 6 and 24 hours of reperfusion (J:152533)
• Il-6 production after vitamin D3 stimulation is significantly reduced (J:166640)
• 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
• reduced TNFalpha levels at 6 and 24 hours after 6 and 24 hours of reperfusion
• 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
• 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
• 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
• 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
• 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) (J:30152)
• increased mortality from GBS infection compared to controls is limited to the first 3 days after challenge (J:30152)
• 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) (J:30152)
• 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 (J:44240)
• treatment with HuC3 restore neutrophil numbers and enhance bacterial clearance to wild-type levels (J:44240)

cardiovascular system
• 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 system
• mice show less evidence of infarction compared to controls

homeostasis/metabolism
• after 70% partial hepatectomy
• reduced levels at 6 and 24 hours after 6 and 24 hours of reperfusion (J:152533)
• Il-6 production after vitamin D3 stimulation is significantly reduced (J:166640)
• lower levels of myeloperoxidase in livers at 6 and 24 hours of reperfusion
• levels lower during reperfusion after ischemia than in controls
• after 70% partial hepatectomy
• 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
• reduced TNFalpha levels at 6 and 24 hours after 6 and 24 hours of reperfusion
• 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
• after CLP less peritoneal mast cells can be recovered from Cr3-deficient mice compared to controls
• 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
• bone marrow cells incubated with 1,25(OH)2 vitamin D3 produce fewer osteoclasts than do cells from controls
• 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
• diameter of GCs are less than that observed in wild-type
• 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

liver/biliary system
• histological evidence of injury after 6 and 24 hours of reperfusion following ischemia
• after 70% partial hepatectomy
• increased steatosis after 70% hepatectomy
• impaired hepatocyte proliferation after 30 minutes of ischemia during 70% partial hepatectomy
• 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
• significant hepatic injury after 30 minutes of ischemia during 70% partial hepatectomy
• impaired regenerative response after 70% hepatectomy

nervous system
• locomotor recovery from spinal cord injury occurs more rapidly than in controls
• slight improvement in tissue at 24 hours aftwr injury but considerably improved relative to controls by 72 hours
• grossly normal at 7 days after injury compared to controls which show marked necrosis and vacuolation in controls at 21 days

skeleton
• bone marrow cells incubated with 1,25(OH)2 vitamin D3 produce fewer osteoclasts than do cells from controls

cellular
• after 70% partial hepatectomy
• impaired hepatocyte proliferation after 30 minutes of ischemia during 70% partial hepatectomy

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
complement component 3 deficiency DOID:8354 OMIM:613779
J:30152


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
09/10/2019
MGI 6.14
The Jackson Laboratory