Phenotypes Associated with This Genotype

Genotype
MGI:3807778

• Allelic Composition: Tox^tm1.1Kay/Tox^tm1.1Kay
• Genetic Background: involves: 129S6/SvEvTac

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

immune system

abnormal CD4-positive T cell differentiation ( J:131287 )

• CD4 T cell development is blocked at the double positive stage 3 step where high surface expression of TCR beta is needed to develop precursors into mature CD4⁺ T cells

• analysis of various developmental markers (Bim, Rag1, Gata3, Zbtb7b) places developmental arrest of CD4 T cells after positive selection of the TCR but before CD4 T cell lineage commitment

• this defect is intrinsic to the T cell precursors as revealed by mixed bone marrow chimera experiments in irradiated wild-type hosts

decreased CD4-positive, alpha-beta T cell number ( J:131287 )

• CD4⁺ and CD4+CD8^lo thymocytes are virtually absent in the thymus

• there are 24- and 16-fold reductions in the frequency and absolute number of splenic CD4⁺ T cells compared to wild-type controls

• splenic CD4⁺ T cells are also CD44⁺ indicating a large expansion of a few CD4 T cells that manage to develop in the thymus

decreased NK T cell number ( J:131287 )

• NKT cells are severely reduced both in the thymus and spleen

abnormal CD4-positive, CD25-positive, alpha-beta regulatory T cell morphology ( J:131287 )

• the frequency of Foxp3⁺ T cells in the thymus is reduced more than 10-fold

• few Foxp3⁺ T cells are found in the spleen with the many of these cells not expression CD4 or CD25

abnormal CD8-positive, alpha beta T cell morphology ( J:131287 )

• 42% of CD8⁺ T cells are also CD44⁺ indicating an expansion of the CD8⁺ T cell population that leaves the thymus

decreased cytotoxic T cell cytolysis ( J:131287 )

• CD8⁺ T cells have a some reduction in cytoxic activity compared to controls

hematopoietic system

abnormal CD4-positive T cell differentiation ( J:131287 )

• CD4 T cell development is blocked at the double positive stage 3 step where high surface expression of TCR beta is needed to develop precursors into mature CD4⁺ T cells

• analysis of various developmental markers (Bim, Rag1, Gata3, Zbtb7b) places developmental arrest of CD4 T cells after positive selection of the TCR but before CD4 T cell lineage commitment

• this defect is intrinsic to the T cell precursors as revealed by mixed bone marrow chimera experiments in irradiated wild-type hosts

decreased CD4-positive, alpha-beta T cell number ( J:131287 )

• CD4⁺ and CD4+CD8^lo thymocytes are virtually absent in the thymus

• there are 24- and 16-fold reductions in the frequency and absolute number of splenic CD4⁺ T cells compared to wild-type controls

• splenic CD4⁺ T cells are also CD44⁺ indicating a large expansion of a few CD4 T cells that manage to develop in the thymus

decreased NK T cell number ( J:131287 )

• NKT cells are severely reduced both in the thymus and spleen

abnormal CD4-positive, CD25-positive, alpha-beta regulatory T cell morphology ( J:131287 )

• the frequency of Foxp3⁺ T cells in the thymus is reduced more than 10-fold

• few Foxp3⁺ T cells are found in the spleen with the many of these cells not expression CD4 or CD25

abnormal CD8-positive, alpha beta T cell morphology ( J:131287 )

• 42% of CD8⁺ T cells are also CD44⁺ indicating an expansion of the CD8⁺ T cell population that leaves the thymus

decreased cytotoxic T cell cytolysis ( J:131287 )

• CD8⁺ T cells have a some reduction in cytoxic activity compared to controls