Phenotypes Associated with This Genotype

Genotype
MGI:3043881

• Allelic Composition: Cd274^tm1Lpc/Cd274^tm1Lpc
• Genetic Background: B6.129S-Cd274^tm1Lpc

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

immune system

decreased T cell apoptosis ( J:89781 )

• homozygotes display reduced apoptosis of SEB-activated CD8⁺ T cells in the liver, but not in the lymph nodes, kidney, or lung

• in an OT-1 TCR transgenic T cell-transfer system, homozygotes display a significantly reduced apoptosis of activated OT-1 CD8⁺ cells in the liver on day 5 after OVA peptide injection (11.2% vs 49.2% in wild-type controls)

• however, no significant differences in intrahepatic CD8⁺ T cell apoptosis are observed in naive homozygotes relative to wild-type controls

increased CD8-positive, alpha-beta T cell number ( J:89781 )

• homozygotes display spontaneous accumulation of CD8⁺ T cells in the liver (average ratio of intrahepatic CD8⁺ to CD4⁺ T cells is equal to 1.6 vs 0.46 in wild-type mice) and kidney (9.4% vs 3.2% in wild-type mice), with only a marginal increase observed in lung (11.6% vs 7.1% in wild-type mice)

• however, numbers of intrahepatic CD4⁺ T cells and B220⁺ B cells are not significantly altered

increased activated T cell number ( J:89781 )

• naive homozygotes show a significant accumulation of activated CD8⁺ T cells in the liver as shown by surface marker expression analysis, with no differences noted in the lymph nodes

• 55.9% of mutant intrahepatic CD8⁺ T cells are CD62L^low relative to 12.7% in wild-type controls

• 85.6% of mutant intrahepatic CD8⁺ T cells are CD45RB^low relative to 12.3% in wild-type controls

• however, no differences in the expression of CD25 or CD44 are observed relative to wild-type controls

abnormal CD8-positive, alpha-beta T cell physiology ( J:89781 )

• following stimulation with staphylococcal enetrotoxin B (SEB), homozygotes show a normal proliferation phase but display impaired deletion of SEB-activated CD8⁺ Vbeta8⁺ T cells in the liver on day 7 of the contraction phase, when SEB-primed T cells are normally reduced by apoptosis

• following transfer of wild-type CD8⁺ OT-1 T cells and subsequent challenge with OVA peptide, homozygotes show significant accumulation and decreased apoptosis of activated CD8⁺ T cells in the liver

increased susceptibility to autoimmune disorder ( J:89781 )

• in a model of experimental (ConA-induced) autoimmune hepatitis, homozygotes display accelerated hepatocyte damage and necrosis, higher serum GTP levels, increased infiltration of mononuclear cells and reduced apoptosis of CD8⁺ T cells in the liver relative to wild-type controls

• 40% of homozygotes die upon induction relative to only 10% of wild-type controls

hematopoietic system

hematopoietic system phenotype ( J:89781 )

N • at 8-12 weeks of age, naive homozygotes display normal T cell populations in the thymus, spleen and lymph nodes relative to wild-type controls

decreased T cell apoptosis ( J:89781 )

• homozygotes display reduced apoptosis of SEB-activated CD8⁺ T cells in the liver, but not in the lymph nodes, kidney, or lung

• in an OT-1 TCR transgenic T cell-transfer system, homozygotes display a significantly reduced apoptosis of activated OT-1 CD8⁺ cells in the liver on day 5 after OVA peptide injection (11.2% vs 49.2% in wild-type controls)

• however, no significant differences in intrahepatic CD8⁺ T cell apoptosis are observed in naive homozygotes relative to wild-type controls

increased CD8-positive, alpha-beta T cell number ( J:89781 )

• homozygotes display spontaneous accumulation of CD8⁺ T cells in the liver (average ratio of intrahepatic CD8⁺ to CD4⁺ T cells is equal to 1.6 vs 0.46 in wild-type mice) and kidney (9.4% vs 3.2% in wild-type mice), with only a marginal increase observed in lung (11.6% vs 7.1% in wild-type mice)

• however, numbers of intrahepatic CD4⁺ T cells and B220⁺ B cells are not significantly altered

increased activated T cell number ( J:89781 )

• naive homozygotes show a significant accumulation of activated CD8⁺ T cells in the liver as shown by surface marker expression analysis, with no differences noted in the lymph nodes

• 55.9% of mutant intrahepatic CD8⁺ T cells are CD62L^low relative to 12.7% in wild-type controls

• 85.6% of mutant intrahepatic CD8⁺ T cells are CD45RB^low relative to 12.3% in wild-type controls

• however, no differences in the expression of CD25 or CD44 are observed relative to wild-type controls

abnormal CD8-positive, alpha-beta T cell physiology ( J:89781 )

• following stimulation with staphylococcal enetrotoxin B (SEB), homozygotes show a normal proliferation phase but display impaired deletion of SEB-activated CD8⁺ Vbeta8⁺ T cells in the liver on day 7 of the contraction phase, when SEB-primed T cells are normally reduced by apoptosis

• following transfer of wild-type CD8⁺ OT-1 T cells and subsequent challenge with OVA peptide, homozygotes show significant accumulation and decreased apoptosis of activated CD8⁺ T cells in the liver

cellular

decreased T cell apoptosis ( J:89781 )

• homozygotes display reduced apoptosis of SEB-activated CD8⁺ T cells in the liver, but not in the lymph nodes, kidney, or lung

• in an OT-1 TCR transgenic T cell-transfer system, homozygotes display a significantly reduced apoptosis of activated OT-1 CD8⁺ cells in the liver on day 5 after OVA peptide injection (11.2% vs 49.2% in wild-type controls)

• however, no significant differences in intrahepatic CD8⁺ T cell apoptosis are observed in naive homozygotes relative to wild-type controls