Mouse Genome Informatics
hm1
    Cd40tm1Kik/Cd40tm1Kik
B6.129P2-Cd40tm1Kik/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
N
• normal thrombogenesis in ferric-chloride-induced injury of mesenteric arterioles (J:75152)
• 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


Mouse Genome Informatics
hm2
    Cd40tm1Kik/Cd40tm1Kik
involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• mice exhibit well-developed thymic medullas (J:173115)
• 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


Mouse Genome Informatics
hm3
    Cd40tm1Kik/Cd40tm1Kik
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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
• 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

immune system
N
• normal numbers and ratios of T and B cells (J:25007)
• 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


Mouse Genome Informatics
cx4
    Cd40tm1Kik/Cd40tm1Kik
Tg(Tnfsf13b)1Fma/?

B6.Cg-Cd40tm1Kik Tg(Tnfsf13b)1Fma
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• the number of splenic marginal zone B cells is increased by about 3-fold
• 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
• B cells exhibit reduced class switching in response to T cell-dependent antigens
• mice are defective in germinal center formation upon after immunization
• 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
• the number of splenic marginal zone B cells is increased by about 3-fold
• 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
• B cells exhibit reduced class switching in response to T cell-dependent antigens
• mice are defective in germinal center formation upon after immunization


Mouse Genome Informatics
cx5
    Cd40tm1Kik/Cd40tm1Kik
Traf3ip2tm1.1Lix/Traf3ip2tm1.1Lix

involves: 129 * 129P2/OlaHsd * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 (J:138560)
• 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 IDRef(s)
NOT Immunodeficiency with Hyper-IgM, Type 1; HIGM1 308230 J:93923


Mouse Genome Informatics
cx6
    Bank1tm1Kuro/Bank1tm1Kuro
Cd40tm1Kik/Cd40tm1Kik

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• increased IgM response and germinal center formation seen in Bank1 single homozygotes are absent in double homozygotes (J:113321)


Mouse Genome Informatics
cx7
    Cd40tm1Kik/Cd40tm1Kik
Tnfsf11tm1Pngr/Tnfsf11tm1Pngr

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 fewer Aire+ medullary epithelial cells (mTEC) compared with wild-type mice
• mice exhibit reduced MHC IIhigh and MHC IIlow medullary thymic 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


Mouse Genome Informatics
cx8
    Cd40tm1Kik/Cd40tm1Kik
Tg(Igh-V-CD40lg)#Tsub/0

involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype


Mouse Genome Informatics
cx9
    Cd40tm1Kik/Cd40tm1Kik
Ltbrtm1Mmat/Ltbrtm1Mmat

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• unlike Ltbrtm1Mmat homozygotes, mice do not exhibit lymphoid cell aggregates (J:173115)
• 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