Phenotypes Associated with This Genotype

Genotype
MGI:2657187

• Allelic Composition: Tnfrsf21^tm1Vmd/Tnfrsf21^tm1Vmd
• Genetic Background: involves: C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

immune system

immune system phenotype ( J:72761 )

N • homozygotes exhibit normal numbers of B cells, neutrophils, NK cells, and monocyte/macrophages in lymphoid organs relative to wild-type controls

increased T cell number ( J:72761 )

• homozygotes display a slight but statistically significant increase in the % of total CD3⁺ T cells in thymus and peripheral blood relative to wild-type controls

• however, no significant differences in thymus size or thymocyte number are observed

increased CD4-positive, alpha-beta T cell number ( J:72761 )

• homozygotes show a ~2-fold increase in CD4⁺ T cell number in peripheral blood relative to wild-type controls

increased CD8-positive, alpha-beta T cell number ( J:72761 )

• homozygotes show a ~2-fold increase in CD8⁺ T cell number in peripheral blood relative to wild-type controls

abnormal cell-mediated immunity ( J:72761 )

• when challenged with protein antigen, mutant T cells hyperproliferate and display a profound polarization towards a Th2 response

• in contrast, Th1-associated responses remain normal

increased T cell proliferation ( J:72761 )

• in vitro, purified CD4⁺ T cells from mutant mice are hyperproliferative in response to stimulation with Con A, anti-CD3 alone, or anti-CD3 plus anti-CD28 relative to wild-type T cells

• after in vitro stimulation of draining lymph node (DLN) cells with KLH, T cells from KLH/CFA-primed homozygotes show an increased proliferative response relative to wild-type cells

• however, mutant splenic T cells and thymocytes display normal susceptibility to activation-induced cell death and death induced by other proapoptotic stimuli, indicating that the hyperproliferative response is independent of apoptosis

increased IgE level ( J:72761 )

• after in vivo challenge with TNP-conjugated KLH, homozygotes show a significant increase in TNP-specific IgE titers relative to wild-type controls

increased IgG1 level ( J:72761 )

• after in vivo challenge with TNP-conjugated KLH, homozygotes show a ~200% increase in TNP-specific IgG1 titers relative to wild-type controls, indicating preferential Th2 cell differentiation and hyperproliferation

increased IgG2a level ( J:72761 )

• after in vivo challenge with TNP-conjugated KLH, homozygotes show a slight increase in TNP-specific IgG2a titers relative to wild-type controls

increased IgM level ( J:72761 )

• after in vivo challenge with TNP-conjugated KLH, homozygotes show a slight increase in TNP-specific IgM titers relative to wild-type controls

abnormal T-helper 2 physiology ( J:72761 )

• after in vitro stimulation of DLN cells with KLH, T cells from KLH/CFA-primed homozygotes show a ~2-fold increase in IL-4 production relative to wild-type cells, indicating polarization towards a Th2 response

• after in vivo challenge with TNP-conjugated KLH, homozygotes show a ~200% increase in TNP-specific IgG1 titers relative to wild-type controls, indicating preferential Th2 cell differentiation and hyperproliferation

• upon activation with anti-CD3 plus anti-CD28, naive mutant CD4⁺ T cells grown in the presence of IL-4 and anti-IFN-gamma secrete significantly higher Th2 cytokine levels (e.g. IL-4) than wild-type cells

increased interferon-gamma secretion ( J:72761 )

• after in vitro stimulation of DLN cells with KLH, T cells from KLH/CFA-primed homozygotes produce significantly higher IFN-gamma levels than wild-type cells

increased interleukin-2 secretion ( J:72761 )

• in vitro, purified CD4⁺ T cells from mutant mice produce significantly higher IL-2 levels than wild-type cells in response to stimulation with Con A, anti-CD3 alone, or anti-CD3 plus anti-CD28

• after in vitro stimulation of DLN cells with KLH, T cells from KLH/CFA-primed homozygotes produce significantly higher IL-2 levels than wild-type cells

increased interleukin-4 secretion ( J:72761 )

• after in vitro stimulation of DLN cells with KLH, T cells from KLH/CFA-primed homozygotes show a ~2-fold increase in IL-4 production relative to wild-type cells, indicating polarization towards a Th2 response

• upon activation with anti-CD3 plus anti-CD28, naive mutant CD4⁺ T cells grown in the presence of IL-4 and anti-IFN-gamma secrete significantly higher IL-4 levels than wild-type cells

hematopoietic system

increased T cell proliferation ( J:72761 )

• in vitro, purified CD4⁺ T cells from mutant mice are hyperproliferative in response to stimulation with Con A, anti-CD3 alone, or anti-CD3 plus anti-CD28 relative to wild-type T cells

• after in vitro stimulation of draining lymph node (DLN) cells with KLH, T cells from KLH/CFA-primed homozygotes show an increased proliferative response relative to wild-type cells

• however, mutant splenic T cells and thymocytes display normal susceptibility to activation-induced cell death and death induced by other proapoptotic stimuli, indicating that the hyperproliferative response is independent of apoptosis

increased T cell number ( J:72761 )

• homozygotes display a slight but statistically significant increase in the % of total CD3⁺ T cells in thymus and peripheral blood relative to wild-type controls

• however, no significant differences in thymus size or thymocyte number are observed

increased CD4-positive, alpha-beta T cell number ( J:72761 )

• homozygotes show a ~2-fold increase in CD4⁺ T cell number in peripheral blood relative to wild-type controls

increased CD8-positive, alpha-beta T cell number ( J:72761 )

• homozygotes show a ~2-fold increase in CD8⁺ T cell number in peripheral blood relative to wild-type controls

increased IgE level ( J:72761 )

• after in vivo challenge with TNP-conjugated KLH, homozygotes show a significant increase in TNP-specific IgE titers relative to wild-type controls

increased IgG1 level ( J:72761 )

• after in vivo challenge with TNP-conjugated KLH, homozygotes show a ~200% increase in TNP-specific IgG1 titers relative to wild-type controls, indicating preferential Th2 cell differentiation and hyperproliferation

increased IgG2a level ( J:72761 )

• after in vivo challenge with TNP-conjugated KLH, homozygotes show a slight increase in TNP-specific IgG2a titers relative to wild-type controls

increased IgM level ( J:72761 )

• after in vivo challenge with TNP-conjugated KLH, homozygotes show a slight increase in TNP-specific IgM titers relative to wild-type controls

abnormal T-helper 2 physiology ( J:72761 )

• after in vitro stimulation of DLN cells with KLH, T cells from KLH/CFA-primed homozygotes show a ~2-fold increase in IL-4 production relative to wild-type cells, indicating polarization towards a Th2 response

• after in vivo challenge with TNP-conjugated KLH, homozygotes show a ~200% increase in TNP-specific IgG1 titers relative to wild-type controls, indicating preferential Th2 cell differentiation and hyperproliferation

• upon activation with anti-CD3 plus anti-CD28, naive mutant CD4⁺ T cells grown in the presence of IL-4 and anti-IFN-gamma secrete significantly higher Th2 cytokine levels (e.g. IL-4) than wild-type cells

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:72761 )

• following stimulation with anti-CD3 plus anti-CD-28 for 48 hrs, purified mutant splenic CD4⁺ T cells show a significant reduction in JNK activity relative to wild-type cells

cellular

increased T cell proliferation ( J:72761 )

• in vitro, purified CD4⁺ T cells from mutant mice are hyperproliferative in response to stimulation with Con A, anti-CD3 alone, or anti-CD3 plus anti-CD28 relative to wild-type T cells

• after in vitro stimulation of draining lymph node (DLN) cells with KLH, T cells from KLH/CFA-primed homozygotes show an increased proliferative response relative to wild-type cells

• however, mutant splenic T cells and thymocytes display normal susceptibility to activation-induced cell death and death induced by other proapoptotic stimuli, indicating that the hyperproliferative response is independent of apoptosis