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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
C4btm1Crr
targeted mutation 1, Michael C Carroll
MGI:1889070
Summary 5 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
C4btm1Crr/C4btm1Crr involves: 129S4/SvJae MGI:5296003
hm2
C4btm1Crr/C4btm1Crr involves: 129S4/SvJae * C57BL/6 MGI:2429659
hm3
C4btm1Crr/C4btm1Crr involves: 129S4/SvJae * C57BL/6J MGI:3663104
cx4
C4btm1Crr/C4btm1Crr
Faslpr/Faslpr
involves: 129S4/SvJae * C57BL/6 * MRL MGI:3800668
cx5
C3tm1Crr/C3tm1Crr
C4btm1Crr/C4btm1Crr
Faslpr/Faslpr
involves: 129S4/SvJae * C57BL/6 * MRL MGI:3800670


Genotype
MGI:5296003
hm1
Allelic
Composition
C4btm1Crr/C4btm1Crr
Genetic
Background
involves: 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
C4btm1Crr mutation (1 available); any C4b mutation (64 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• reduced neutrophil infiltration of glomerulus relative to controls when injected with 0.5 mg and with 1.0mg of anti-glomerular basement membrane antiserum

homeostasis/metabolism
• thrombus formation only moderately reduced

immune system
• reduced neutrophil infiltration of glomerulus relative to controls when injected with 0.5 mg and with 1.0mg of anti-glomerular basement membrane antiserum
• mice show some protection from intranasal infection with the mouse-adapted SARS-CoV MA15 , showing less weight loss than in wild-type controls but more weight loss than in C3tm1Crr homozygotes




Genotype
MGI:2429659
hm2
Allelic
Composition
C4btm1Crr/C4btm1Crr
Genetic
Background
involves: 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
C4btm1Crr mutation (1 available); any C4b mutation (64 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• increased mortality from GBS infection compared to controls is limited to the first 3 days after challenge
• mice challenged with group B Streptococci (GBS) infection become bacteremic within 3 days and die or clear bacteria and survive; C4b-deficient mice challenged with GBS infection showed a decreased LD50 dose compared to immunocompetent controls (LD50 dose: control 6.3 x 104 vs. 2.4 x 103 in C4b-deficient mice)
• caecal ligation and puncture (CLP) causes greater mortality in mutants than wild-type in the first 24 hours after CLP (100 vs 20% mortality)

immune system
N
• serum from C4-deficient mice has similar antibody-mediated opsonophagocytic killing of GBS to control serum (J:30152)
• secondary immune responses are similar in wild-type and mutant mice, so helper T cell function is normal (J:64282)
• B cells from deficient mice show normal proliferative effects in response to surface IgM crosslinking (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
• diameter of GCs are less than that observed in wild-type
• 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
• in response to immunization with bacteriophage (phiX174), a T cell dependent antigen, C4b-deficient mice mount a weak Ig M response but fail to switch to IgG
• 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
• when pregnant dams are immunized with immune rabbit serum, pups are protected against lethal challenge on day 2 of life because of transfer of maternal antibodies to the pups (15/16 pups survive, similar to controls)
• increased mortality from GBS infection compared to controls is limited to the first 3 days after challenge
• mice challenged with group B Streptococci (GBS) infection become bacteremic within 3 days and die or clear bacteria and survive; C4b-deficient mice challenged with GBS infection showed a decreased LD50 dose compared to immunocompetent controls (LD50 dose: control 6.3 x 104 vs. 2.4 x 103 in C4b-deficient mice)

homeostasis/metabolism
N
• response to renal ischemia reperfusion injury is the same as in wild-type mice

hematopoietic system
• 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

cardiovascular system
• upeon reperfusion of ischemic intestine (jejunum), permeability index (PI) of injured C4b-deficient mice is reduced compared to control treated wild-type (PI of 2.20 vs 3.26 in controls)

digestive/alimentary system
• mice show less evidence of infarction compared to controls

liver/biliary system
• 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




Genotype
MGI:3663104
hm3
Allelic
Composition
C4btm1Crr/C4btm1Crr
Genetic
Background
involves: 129S4/SvJae * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
C4btm1Crr mutation (1 available); any C4b mutation (64 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• at 10 months of age, spleens of C4b-deficient females are enlarged with an average weight of 368 mg compared to controls which are ~100mg; most females have spleens 2-fold larger by weight, and 1/3 have spleens 4 times the average control weight

immune system
• at 10 months of age, spleens of C4b-deficient females are enlarged with an average weight of 368 mg compared to controls which are ~100mg; most females have spleens 2-fold larger by weight, and 1/3 have spleens 4 times the average control weight
• numbers are increased 4-fold over controls
• numbers are increased 2-fold over controls
• spontaneous germinal center formation is observed in C4b-deficient mice
• clearance of soluble immune complexes (IC) injected into mice is delayed initially in C4b-deficient mice, resulting in a 2- to 3-fold increase in circulating IC levels compared to C2-deficient or B6.129-Ighb controls
• levels remain high for at least 70 minutes
• by 5-6 months of age, >50% of C4b-deficient females (on Ighb haplotype homozygous background) have antinuclear antibody (ANA) levels comparable to Fas-deficient mice
• males have ANA levels higher (but not significant) than controls
• in 10-month old females, ANA levels as high as 1:30000 are present
• IgG autoantibody titers against dsDNA are increased over controls in females at 10 months of age
• IgG autoantibody titers against ss-DNA are increased over controls in females at 10 months of age
• ~50% of 10-month old female C4b-deficient mice show glomerulonephritis but no male do

renal/urinary system
• marked enlargement with hypercellularity is observed in the glomeruli of females at 10 months
• ~50% of 10-month old female C4b-deficient mice show glomerulonephritis but no male do
• many female mice display mesangial deposition of immune complexes (ICs) of IgG and C3

hematopoietic system
• at 10 months of age, spleens of C4b-deficient females are enlarged with an average weight of 368 mg compared to controls which are ~100mg; most females have spleens 2-fold larger by weight, and 1/3 have spleens 4 times the average control weight
• numbers are increased 4-fold over controls
• numbers are increased 2-fold over controls
• spontaneous germinal center formation is observed in C4b-deficient mice




Genotype
MGI:3800668
cx4
Allelic
Composition
C4btm1Crr/C4btm1Crr
Faslpr/Faslpr
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * MRL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
C4btm1Crr mutation (1 available); any C4b mutation (64 available)
Faslpr mutation (39 available); any Fas mutation (76 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• spleen mass is significantly increased relative to C3 /Faslpr or single Faslpr mutants at 17 weeks of age

immune system
• spleen mass is significantly increased relative to C3 /Faslpr or single Faslpr mutants at 17 weeks of age
• lymph node mass is increased relative to C3-null, Faslpr or single Faslpr mutants at 13 and 17 weeks of age
• frequency of antibody-secreting cells (ASCs) or antibody-forming cells (AFCs) is significantly increased in spleen and bone marrow compared to C3-deficient Fas mutants
• titers of serum ANA are significantly increased at 10, 13, and 17 weeks
• anti-dsDNA titers are elevated significantly at 17 weeks

hematopoietic system
• spleen mass is significantly increased relative to C3 /Faslpr or single Faslpr mutants at 17 weeks of age

renal/urinary system
• increased IgG deposition relative to C3/Fas mutants is observed in kidney sections
• more severe glomerular abnormalities are observed relative to C3/Fas mutants




Genotype
MGI:3800670
cx5
Allelic
Composition
C3tm1Crr/C3tm1Crr
C4btm1Crr/C4btm1Crr
Faslpr/Faslpr
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * MRL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
C3tm1Crr mutation (4 available); any C3 mutation (68 available)
C4btm1Crr mutation (1 available); any C4b mutation (64 available)
Faslpr mutation (39 available); any Fas mutation (76 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• spleen mass is significantly increased relative to C3-null, Faslpr or single Faslpr mutants at 17 weeks of age

immune system
• spleen mass is significantly increased relative to C3-null, Faslpr or single Faslpr mutants at 17 weeks of age
• lymph node mass is increased relative to C3-null, Faslpr or single Faslpr mutants at 10 and 13 weeks of age
• frequency of antibody-secreting cells (ASCs) or antibody-forming cells (AFCs) is significantly increased in spleen, bone marrow, and lymph nodes compared to C3-deficient Fas mutants or single Faslpr mutants
• titers of serum ANA are significantly increased at 10 and 17 weeks, compared to single-deficient mice
• anti-dsDNA titers are elevated significantly relative to C4, Fas double mutants

hematopoietic system
• spleen mass is significantly increased relative to C3-null, Faslpr or single Faslpr mutants at 17 weeks of age

renal/urinary system
• increased IgG deposition relative to C3/Fas mutants is observed in kidney sections; deposition is similar to C4/Fas mutants
• more severe glomerular abnormalities are observed relative to C3/Fas mutants, and pathology is similar to that of C4/Fas double mutants





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last database update
10/19/2021
MGI 6.17
The Jackson Laboratory