Mouse Genome Informatics
hm1
    Tnfrsf9tm1Byk/Tnfrsf9tm1Byk
B6.Cg-Tnfrsf9tm1Byk
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• absolute numbers of granulocyte-macrophage, erythroid, and multipotential progenitor cells in the bone marrow, blood, and spleen are higher in mutants than wild-type mice
• proliferation of splenocytes/T-cells is increased compared to wild-type mice when stimulated with anti-CD3 mAb and ConA
• 2-3-fold decrease in IgG2a in response to keyhole limpet hemocyanin (KLH) immunization
• 2-3-fold decrease in IgG3 in response to KLH immunization
• mutants show significantly decreased cytotoxic T lymphocyte activity to vesicular stomatitis virus

immune system
• proliferation of splenocytes/T-cells is increased compared to wild-type mice when stimulated with anti-CD3 mAb and ConA
• 2-3-fold decrease in IgG2a in response to keyhole limpet hemocyanin (KLH) immunization
• 2-3-fold decrease in IgG3 in response to KLH immunization
• mutants show significantly decreased cytotoxic T lymphocyte activity to vesicular stomatitis virus
• decrease in IFN-gamma production in response to KLH immunization
• moderate decrease in IFN-gamma secretion from T cells
• moderate decrease in IL-2 secretion from T cells
• significant decrease in IL-4 secretion from T cells


Mouse Genome Informatics
hm2
    Tnfrsf9tm1Byk/Tnfrsf9tm1Byk
C.Cg-Tnfrsf9tm1Byk
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• splenocytes show increased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA
• absolute numbers of granulocyte-macrophage, erythroid, and multipotential progenitor cells in the bone marrow, blood, and spleen are higher in mutants than wild-type mice
• proliferation of splenocytes/T-cells is increased compared to wild-type mice when stimulated with anti-CD3 mAb and ConA
• in naive mice
• 2-3-fold decrease in IgG2a in response to keyhole limpet hemocyanin (KLH) immunization
• in naive mice
• in naive mice
• 2-3-fold decrease in IgG3 in response to KLH immunization
• Vesicular stomatitis virus-specific cytotoxic T lymphocyte responses and plaque reduction neutralizing ability is reduced

immune system
• splenocytes show increased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA
• proliferation of splenocytes/T-cells is increased compared to wild-type mice when stimulated with anti-CD3 mAb and ConA
• in naive mice
• 2-3-fold decrease in IgG2a in response to keyhole limpet hemocyanin (KLH) immunization
• in naive mice
• in naive mice
• 2-3-fold decrease in IgG3 in response to KLH immunization
• Vesicular stomatitis virus-specific cytotoxic T lymphocyte responses and plaque reduction neutralizing ability is reduced
• decrease in IFN-gamma production in response to KLH immunization
• moderate decrease in IFN-gamma secretion from T cells
• following ConA stimulation
• moderate decrease in IL-2 secretion from T cells
• significant decrease in IL-4 secretion from T cells

cellular
• splenocytes show increased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA


Mouse Genome Informatics
cx3
    Cd28tm1Pjl/Cd28tm1Pjl
Tnfrsf9tm1Byk/Tnfrsf9tm1Byk

either: B6.Cg-Cd28tm1Pjl Tnfrsf9tm1Byk or C.Cg-Cd28tm1Pjl Tnfrsf9tm1Byk
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• splenocytes show decreased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA
• mutants are incapable of undergoing Ig class switch and fail to mount anti-DNP responses of IgG1, IgG2a and IgM
• naive mutants exhibit decreased IgG1 levels and fail to mount anti-DNP responses of IgG1
• naive mutants exhibit decreased IgG2a levels and fail to mount anti-DNP responses of IgG2a
• mutants fail to mount anti-DNP responses of IgM and secrete reduced levels of IgM in response to a TD-antigen
• Vesicular stomatitis virus-specific cytotoxic T lymphocyte responses and plaque reduction neutralizing ability is reduced
• mutants exhibit significantly suppressed contact hypersensitivity to FITC and DNFB
• following ConA stimulation

hematopoietic system
• splenocytes show decreased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA
• mutants are incapable of undergoing Ig class switch and fail to mount anti-DNP responses of IgG1, IgG2a and IgM
• naive mutants exhibit decreased IgG1 levels and fail to mount anti-DNP responses of IgG1
• naive mutants exhibit decreased IgG2a levels and fail to mount anti-DNP responses of IgG2a
• mutants fail to mount anti-DNP responses of IgM and secrete reduced levels of IgM in response to a TD-antigen
• Vesicular stomatitis virus-specific cytotoxic T lymphocyte responses and plaque reduction neutralizing ability is reduced

cellular
• splenocytes show decreased cellular proliferation compared to wild-type mice when stimulated with anti-CD3 or ConA


Mouse Genome Informatics
cx4
    Faslpr/Faslpr
Tnfrsf9tm1Byk/Tnfrsf9tm1Byk

MRL.Cg-Tnfrsf9tm1Byk Faslpr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• by 5 months, 80% mortality is observed compared to 40% in Tnfrsf9-sufficient, Fas-null mice; by 4 months, mice become increasingly moribund and display reduced activity

hematopoietic system
N
• CD8beta+ T cells are not altered in number at any age (J:127197)
• percentages of B-1 (B220+ CD5+) cells are increased significantly in peritoneums and slightly higher in spleens
• percentages of B-2( B220+ CD5-) cells are increased significantly in peritoneums and slightly higher in spleens
• 3- and 5-month old mice show elevated CD4+ T cell numbers in lacrimal glands (J:126929)
• mice display early increases in CD4+ T cells in spleen, and numbers keep rising (J:127197)
• in lacrimal glands, DN T cell percentages are about 2-fold greater than in wild-type Tnfrsf9, Fas lpr controls; similar increases are seen in spleen and salivary glands (J:126929)
• increased proportion seen in spleen compared to Tnfrsf9-sufficient, Fas-null mice (J:127197)
• significant enlargement of axillary lymph nodes is seen at 5 months compared to Tnfrsf9-wt, Fas-null mice
• greatly increased germinal center formation is observed compared to Tnfrsf9-sufficient, Fas-null mice
• circulating titres are elevated compared with compared to Tnfrsf9-sufficient, Fas-null mice

immune system
• extensive and early inflammation is observed compared with control wild-type Tnfrsf9, Fas lpr homozygotes
• by 3 months, extensive mononuclear cell infiltration is observed, becoming intense by 5 months while controls show no infiltrate at 1 month, mimimal inflammatory lesions at 3 months and extensive, although less severe than double mutants, infiltrates by 5 months of age
• percentages of B-1 (B220+ CD5+) cells are increased significantly in peritoneums and slightly higher in spleens
• percentages of B-2( B220+ CD5-) cells are increased significantly in peritoneums and slightly higher in spleens
• 3- and 5-month old mice show elevated CD4+ T cell numbers in lacrimal glands (J:126929)
• mice display early increases in CD4+ T cells in spleen, and numbers keep rising (J:127197)
• in lacrimal glands, DN T cell percentages are about 2-fold greater than in wild-type Tnfrsf9, Fas lpr controls; similar increases are seen in spleen and salivary glands (J:126929)
• increased proportion seen in spleen compared to Tnfrsf9-sufficient, Fas-null mice (J:127197)
• significant enlargement of axillary lymph nodes is seen at 5 months compared to Tnfrsf9-wt, Fas-null mice
• greatly increased germinal center formation is observed compared to Tnfrsf9-sufficient, Fas-null mice
• circulating titres are elevated compared with compared to Tnfrsf9-sufficient, Fas-null mice
• significant enlargement at 5 months compared to Tnfrsf9-wt, Fas-null mice
• in lacrimal glands, increased levels of Il-4 are detected compared to controls
• phenotypic manifestations are increased relative to Faslpr homozygotes
• serum titres of anti-nuclear IgG1/2a are increased at 3 and 5 months
• anti-DNA antibody production is increased compared to Tnfrsf9-sufficient, Fas-null mice

renal/urinary system
• increased immunoglobulin deposits are detected in kidneys compared to controls
• mice show exacerbated renal injury, with increased glomerular infiltrates
• IgG and C3 depositions in kidneys are increased compared with Tnfrsf9-sufficient, Fas-null mice

craniofacial
• from 4 months of age, >60% of mice display progressive erosion of pinnae

hearing/vestibular/ear
• from 4 months of age, >60% of mice display progressive erosion of pinnae

endocrine/exocrine glands
• more apoptotic cells are detected relative to wild-type Tnfrsf9, Fas lpr controls
• increased deposits of IgG1, but not IgG2a are detected in lacrimal glands at 3 and 5 months
• extensive and early inflammation is observed compared with control wild-type Tnfrsf9, Fas lpr homozygotes
• by 3 months, extensive mononuclear cell infiltration is observed, becoming intense by 5 months while controls show no infiltrate at 1 month, mimimal inflammatory lesions at 3 months and extensive, although less severe than double mutants, infiltrates by 5 months of age

vision/eye
• more apoptotic cells are detected relative to wild-type Tnfrsf9, Fas lpr controls
• increased deposits of IgG1, but not IgG2a are detected in lacrimal glands at 3 and 5 months
• extensive and early inflammation is observed compared with control wild-type Tnfrsf9, Fas lpr homozygotes
• by 3 months, extensive mononuclear cell infiltration is observed, becoming intense by 5 months while controls show no infiltrate at 1 month, mimimal inflammatory lesions at 3 months and extensive, although less severe than double mutants, infiltrates by 5 months of age

integument
• by 5 months, skin lesions around tip of nose and around ears are more pronounced than in Tnfrsf9-wt, Fas-null mice

growth/size/body
• from 4 months of age, >60% of mice display progressive erosion of pinnae