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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Cd40tm1Kik
targeted mutation 1, Hitoshi Kikutani
MGI:1857457
Summary 9 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Cd40tm1Kik/Cd40tm1Kik B6.129P2-Cd40tm1Kik/J MGI:3035906
hm2
Cd40tm1Kik/Cd40tm1Kik involves: 129P2/OlaHsd MGI:5013462
hm3
Cd40tm1Kik/Cd40tm1Kik involves: 129P2/OlaHsd * C57BL/6 MGI:3035907
cx4
Cd40tm1Kik/Cd40tm1Kik
Tg(Tnfsf13b)1Fma/?
B6.Cg-Cd40tm1Kik Tg(Tnfsf13b)1Fma MGI:3841106
cx5
Cd40tm1Kik/Cd40tm1Kik
Traf3ip2tm1.1Lix/Traf3ip2tm1.1Lix
involves: 129 * 129P2/OlaHsd * BALB/c MGI:3511170
cx6
Bank1tm1Kuro/Bank1tm1Kuro
Cd40tm1Kik/Cd40tm1Kik
involves: 129P2/OlaHsd MGI:3687154
cx7
Cd40tm1Kik/Cd40tm1Kik
Tnfsf11tm1Pngr/Tnfsf11tm1Pngr
involves: 129P2/OlaHsd MGI:5013467
cx8
Cd40tm1Kik/Cd40tm1Kik
Tg(Igh-V-CD40lg)#Tsub/0
involves: 129P2/OlaHsd * C57BL/6 MGI:4461234
cx9
Cd40tm1Kik/Cd40tm1Kik
Ltbrtm1Mmat/Ltbrtm1Mmat
involves: 129P2/OlaHsd * C57BL/6 * CBA MGI:5013463


Genotype
MGI:3035906
hm1
Allelic
Composition
Cd40tm1Kik/Cd40tm1Kik
Genetic
Background
B6.129P2-Cd40tm1Kik/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd40tm1Kik mutation (10 available); any Cd40 mutation (21 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
N
• normal thrombogenesis in ferric-chloride-induced injury of mesenteric arterioles
• reduced number of rolling platelets and 50% attenuation in platelet adhesion following 1 hour of middle cerebral artery occlusion and 4 hours of reperfusion

immune system
• impaired production of IL-12 after Mycobacterium tuberculosis infection and after incubation with Hsp7
• impaired priming of IFN-gamma producing T cells
• increased susceptibility to aerosol Mycobacterium tuberculosis infection
• increased bacterial loads in lung and spleen
• 40% of infected mice moribund 3 - 4 weeks postinfection

homeostasis/metabolism
• reduced number of rolling platelets and 50% attenuation in platelet adhesion following 1 hour of middle cerebral artery occlusion and 4 hours of reperfusion
• significantly reduced infarct volumes

nervous system
• significantly reduced infarct volumes

skeleton
• significantly reduced
• significantly reduced
• significantly reduced




Genotype
MGI:5013462
hm2
Allelic
Composition
Cd40tm1Kik/Cd40tm1Kik
Genetic
Background
involves: 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd40tm1Kik mutation (10 available); any Cd40 mutation (21 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
N
• mice exhibit well-developed thymic medullas
• NP-CG immunized mice fail to generate NP-specific IgG1+B cells at day 7
• NP-CG immunized mice fail to generate NP-specific germinal center B cells

hematopoietic system
• NP-CG immunized mice fail to generate NP-specific IgG1+B cells at day 7
• NP-CG immunized mice fail to generate NP-specific germinal center B cells




Genotype
MGI:3035907
hm3
Allelic
Composition
Cd40tm1Kik/Cd40tm1Kik
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd40tm1Kik mutation (10 available); any Cd40 mutation (21 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• in non-SPF facilities compared to wild-type controls
• failed to form
• reduced production of IgG1, IgG2a, IgG2b, IgG3, IgA, IgE in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• response to thymus-independent (TI) antigens was in tact
• decreased serum concentrations in unimmunized mice
• reduced production in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• reduced production in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• decreased serum concentrations in unimmunized mice
• reduced production of IgG1 in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• decreased serum concentrations of IgG1 in unimmunized mice
• reduced production of IgG2a in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• decreased serum concentrations of IgG2a in unimmunized mice
• reduced production of IgG2b in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• decreased serum concentrations of IgG2b in unimmunized mice
• reduced production of IgG3 in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• IgG3 serum concentrations in unimmunized mice are not decreased

immune system
N
• normal numbers and ratios of T and B cells
• in non-SPF facilities compared to wild-type controls
• failed to form
• in model of accelerated anti-glomerular basement membrane antibody-mediated glomerulonephritis
• deposition of IgG and complement in glomeruli not observed
• glomeruli almost normal
• fibrin deposition in glomeruli not observed
• failure to induce proteinuria
• reduced production of IgG1, IgG2a, IgG2b, IgG3, IgA, IgE in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• response to thymus-independent (TI) antigens was in tact
• reduced production in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• decreased serum concentrations in unimmunized mice
• reduced production in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• decreased serum concentrations in unimmunized mice
• reduced production of IgG1 in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• decreased serum concentrations of IgG1 in unimmunized mice
• reduced production of IgG2a in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• decreased serum concentrations of IgG2a in unimmunized mice
• reduced production of IgG2b in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• decreased serum concentrations of IgG2b in unimmunized mice
• reduced production of IgG3 in response to thymus-dependent (TD) antigen, dintrophenol-conjugated ovalbumin
• IgG3 serum concentrations in unimmunized mice are not decreased




Genotype
MGI:3841106
cx4
Allelic
Composition
Cd40tm1Kik/Cd40tm1Kik
Tg(Tnfsf13b)1Fma/?
Genetic
Background
B6.Cg-Cd40tm1Kik Tg(Tnfsf13b)1Fma
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd40tm1Kik mutation (10 available); any Cd40 mutation (21 available)
Tg(Tnfsf13b)1Fma mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• B cells exhibit reduced class switching in response to T cell-dependent antigens
• the number of splenic marginal zone B cells is increased by about 3-fold
• mice are defective in germinal center formation upon after immunization
• B cells have a vigorous response to T cell independent antigens producing much higher levels of antigen-specific IgG1, IgG2a, IgG2b, IgG3, and IgA class antibodies than controls
• anti-dsDNA antibodies of the IgM class, IgA class, and all IgG subclasses are found in circulation
• titers of these auto-antibodies increase with age
• kidneys of 10-month old mice have necrotic lesions
• immunohistology of kidneys with severe lesions reveal numerous glomerular deposits of IgG

renal/urinary system
• all 8-month old mice have proteinuria in their urine at 100-300 mg/dl concentration
• kidneys of 10-month old mice have necrotic lesions
• immunohistology of kidneys with severe lesions reveal numerous glomerular deposits of IgG

homeostasis/metabolism
• all 8-month old mice have proteinuria in their urine at 100-300 mg/dl concentration

hematopoietic system
• B cells exhibit reduced class switching in response to T cell-dependent antigens
• the number of splenic marginal zone B cells is increased by about 3-fold
• mice are defective in germinal center formation upon after immunization
• B cells have a vigorous response to T cell independent antigens producing much higher levels of antigen-specific IgG1, IgG2a, IgG2b, IgG3, and IgA class antibodies than controls




Genotype
MGI:3511170
cx5
Allelic
Composition
Cd40tm1Kik/Cd40tm1Kik
Traf3ip2tm1.1Lix/Traf3ip2tm1.1Lix
Genetic
Background
involves: 129 * 129P2/OlaHsd * BALB/c
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd40tm1Kik mutation (10 available); any Cd40 mutation (21 available)
Traf3ip2tm1.1Lix mutation (0 available); any Traf3ip2 mutation (20 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes
• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes
• Tnfsf13b (BAFF) stimulation results in enhanced B cell survival compared to single Cd40 mutants

immune system
N
• double mutants do not exhibit production of anti-SSA/Ro and anti-SSB/La autoantibodies in response to recombinant SSA/Ro and SSB/La antigens, as seen in Traf3ip2 single homozygotes
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• double mutants exhibit an increase in peripheral B cell populations compared to Cd40 single homozygotes
• enlargement of the spleen is reduced compared to Traf3ip2 single homozygotes
• immunoglobulin levels are normal unlike in Traf3ip2 single homozygotes
• Tnfsf13b (BAFF) stimulation results in enhanced B cell survival compared to single Cd40 mutants
• enlargement of the lymph nodes is reduced compared to Traf3ip2 single homozygotes

Mouse Models of Human Disease
OMIM ID Ref(s)
NOT Immunodeficiency with Hyper-IgM, Type 1; HIGM1 308230 J:93923




Genotype
MGI:3687154
cx6
Allelic
Composition
Bank1tm1Kuro/Bank1tm1Kuro
Cd40tm1Kik/Cd40tm1Kik
Genetic
Background
involves: 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bank1tm1Kuro mutation (0 available); any Bank1 mutation (27 available)
Cd40tm1Kik mutation (10 available); any Cd40 mutation (21 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
N
• increased IgM response and germinal center formation seen in Bank1 single homozygotes are absent in double homozygotes




Genotype
MGI:5013467
cx7
Allelic
Composition
Cd40tm1Kik/Cd40tm1Kik
Tnfsf11tm1Pngr/Tnfsf11tm1Pngr
Genetic
Background
involves: 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd40tm1Kik mutation (10 available); any Cd40 mutation (21 available)
Tnfsf11tm1Pngr mutation (0 available); any Tnfsf11 mutation (18 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• mice exhibit reduced MHC IIhigh and MHC IIlow medullary thymic epithelial cells (mTEC) compared with wild-type mice
• mice exhibit fewer Aire+ medullary epithelial cells (mTEC) compared with wild-type mice

hematopoietic system
• mice exhibit reduced MHC IIhigh and MHC IIlow medullary thymic epithelial cells (mTEC) compared with wild-type mice
• mice exhibit fewer Aire+ medullary epithelial cells (mTEC) compared with wild-type mice

endocrine/exocrine glands
• mice exhibit reduced MHC IIhigh and MHC IIlow medullary thymic epithelial cells (mTEC) compared with wild-type mice
• mice exhibit fewer Aire+ medullary epithelial cells (mTEC) compared with wild-type mice




Genotype
MGI:4461234
cx8
Allelic
Composition
Cd40tm1Kik/Cd40tm1Kik
Tg(Igh-V-CD40lg)#Tsub/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd40tm1Kik mutation (10 available); any Cd40 mutation (21 available)
Tg(Igh-V-CD40lg)#Tsub mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype




Genotype
MGI:5013463
cx9
Allelic
Composition
Cd40tm1Kik/Cd40tm1Kik
Ltbrtm1Mmat/Ltbrtm1Mmat
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd40tm1Kik mutation (10 available); any Cd40 mutation (21 available)
Ltbrtm1Mmat mutation (1 available); any Ltbr mutation (15 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
N
• unlike Ltbrtm1Mmat homozygotes, mice do not exhibit lymphoid cell aggregates
• mice exhibit fewer MHC IIlow medullary thymic epithelial cells compared to in wild-type mice
• mice exhibit fewer Aire+ medullary epithelial cells compared with wild-type mice
• medullary areas are smaller in size and less frequently connected to each other than in wild-type mice

hematopoietic system
• mice exhibit fewer MHC IIlow medullary thymic epithelial cells compared to in wild-type mice
• mice exhibit fewer Aire+ medullary epithelial cells compared with wild-type mice
• medullary areas are smaller in size and less frequently connected to each other than in wild-type mice

endocrine/exocrine glands
• mice exhibit fewer MHC IIlow medullary thymic epithelial cells compared to in wild-type mice
• mice exhibit fewer Aire+ medullary epithelial cells compared with wild-type mice
• medullary areas are smaller in size and less frequently connected to each other than in wild-type mice





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last database update
05/17/2016
MGI 6.03
The Jackson Laboratory