Analysis Tools
immune system
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• much less susceptible to experimental autoimmune encephalitis induced by antibodies to Mog
• primary immune response to Mog is normal
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Allele Symbol Allele Name Allele ID |
Tg(Lck-cre)1Cwi transgene insertion 1, Christopher B Wilson MGI:2448686 |
| Summary |
81 genotypes |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• much less susceptible to experimental autoimmune encephalitis induced by antibodies to Mog
• primary immune response to Mog is normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• anti-CD3 and anti-CD28 stimulation enhances proliferation compared to wild-type
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• anti-CD3 and anti-CD28 stimulation enhances cytokine production by T cells
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• Ifng secretion by T cells upon anti-CD3 and anti-CD28 stimulation is enhanced
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• IL-2 secretion by T cells upon anti-CD3 and anti-CD28 stimulation is enhanced
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• anti-CD3 and anti-CD28 stimulation enhances proliferation compared to wild-type
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• anti-CD3 and anti-CD28 stimulation enhances proliferation compared to wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• total thymocyte numbers are slightly reduced compared to in wild-type mice
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• DN4 cells are completely missing
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• immature single positive cells are lost
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• total thymocyte numbers are slightly reduced compared to in wild-type mice
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• DN4 cells are completely missing
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• immature single positive cells are lost
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• total thymocyte numbers are slightly reduced compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• unlike in Smarca4tm1Grc/Smarca4tm1Grc Tg(Lck-cre)1Cwi mice, a CD4-CD8+ population is not observed
• 25% of the post-DN3 population is composed of CD4-DN4 cells compared to 9% in Smarca4tm1Grc/Smarca4tm1Grc Tg(Lck-cre)1Cwi Tg(LCKprBCL2L1)12Sjk mice
• 39% of the post-DN3 population is composed of CD4+DN4 cells compared to 52% in Smarca4tm1Grc/Smarca4tm1Grc Tg(Lck-cre)1Cwi Tg(LCKprBCL2L1)12Sjk mice
• mice exhibit two CD4+ populations with different levels of CD4 expression
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• unlike in Smarca4tm1Grc/Smarca4tm1Grc Tg(Lck-cre)1Cwi mice, a CD4-CD8+ population is not observed
• 25% of the post-DN3 population is composed of CD4-DN4 cells compared to 9% in Smarca4tm1Grc/Smarca4tm1Grc Tg(Lck-cre)1Cwi Tg(LCKprBCL2L1)12Sjk mice
• 39% of the post-DN3 population is composed of CD4+DN4 cells compared to 52% in Smarca4tm1Grc/Smarca4tm1Grc Tg(Lck-cre)1Cwi Tg(LCKprBCL2L1)12Sjk mice
• mice exhibit two CD4+ populations with different levels of CD4 expression
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 38% of the post-DN3 population is composed of CD4+CD8- cells compared to 14% in Smarca4tm1Grc/Smarca4tm1Grc Tg(Lck-cre)1Cwi mice
• unlike in Smarca4tm1Grc/Smarca4tm1Grc Tg(Lck-cre)1Cwi mice, a CD4-CD8+ population analogous to immature single positive cells is not observed
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• thymocyte numbers are reduced 13-fold compared to in wild-type mice
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• post-DN3 T cells are reduced compared to in wild-type mice
• however, DN3 cellularity is normal
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• 38% of the post-DN3 population is composed of CD4+CD8- cells compared to 14% in Smarca4tm1Grc/Smarca4tm1Grc Tg(Lck-cre)1Cwi mice
• unlike in Smarca4tm1Grc/Smarca4tm1Grc Tg(Lck-cre)1Cwi mice, a CD4-CD8+ population analogous to immature single positive cells is not observed
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• thymocyte numbers are reduced 13-fold compared to in wild-type mice
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• post-DN3 T cells are reduced compared to in wild-type mice
• however, DN3 cellularity is normal
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• thymocyte numbers are reduced 13-fold compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• thymus cellularity is only 10-30% of controls
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• double-negative thymocyte numbers are similar to wild-type but the distribution of the sub-populations differs
• these DN3 cells have less proliferation suggesting a partial block in development
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• double-positive thymocyte numbers are decreased compared to wild-type while double-negative numbers are close to normal
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• single-positive thymocyte numbers are decreased compared to controls
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• thymus cellularity is only 10-30% of controls
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• double-negative thymocyte numbers are similar to wild-type but the distribution of the sub-populations differs
• these DN3 cells have less proliferation suggesting a partial block in development
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• double-positive thymocyte numbers are decreased compared to wild-type while double-negative numbers are close to normal
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• single-positive thymocyte numbers are decreased compared to controls
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• thymus cellularity is only 10-30% of controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• thymus cellularity is only 10-30% of controls
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• double-negative thymocyte numbers are similar to wild-type but the distribution of the sub-populations differs
• mice have a 83% DN3 stage thymocytes compared to 48% in normal mice, with a
concomitant decrease in the DN4 stage thymocytes (46% in normal versus 8% in double-transgenic mice)
• these DN3 cells have less proliferation suggesting a partial block in development
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• double-positive thymocyte numbers are decreased compared to wild-type while double-negative numbers are close to normal
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• single-positive thymocyte numbers are decreased compared to controls
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• thymus cellularity is only 10-30% of controls
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• double-negative thymocyte numbers are similar to wild-type but the distribution of the sub-populations differs
• mice have a 83% DN3 stage thymocytes compared to 48% in normal mice, with a
concomitant decrease in the DN4 stage thymocytes (46% in normal versus 8% in double-transgenic mice)
• these DN3 cells have less proliferation suggesting a partial block in development
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• double-positive thymocyte numbers are decreased compared to wild-type while double-negative numbers are close to normal
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• single-positive thymocyte numbers are decreased compared to controls
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• thymus cellularity is only 10-30% of controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• a 25% reduction in proliferation of both DN4 and DP thymocytes
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• 50% reduction in total thymocyte numbers
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• decrease in the number and percentage of DN4 cells and an increase in the DN3:DN4 ratio
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• while the total number is reduced the percentage of DN cells is increased
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• decrease in the number of CD4+ thymocytes
• however, the number of peripheral CD4+ lymph node T cells is not decreased
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• however, the number of peripheral CD8+ lymph node T cells is not decreased
• decrease in the number of CD8+ thymocytes
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• decreased by 50%
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• a 25% reduction in proliferation of both DN4 and DP thymocytes
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• 50% reduction in total thymocyte numbers
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• decrease in the number and percentage of DN4 cells and an increase in the DN3:DN4 ratio
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• while the total number is reduced the percentage of DN cells is increased
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• decrease in the number of CD4+ thymocytes
• however, the number of peripheral CD4+ lymph node T cells is not decreased
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• decrease in the number of CD8+ thymocytes
• however, the number of peripheral CD8+ lymph node T cells is not decreased
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• decreased by 50%
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• 50% reduction in total thymocyte numbers
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• decrease in the number and percentage of DN4 cells and an increase in the DN3:DN4 ratio
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• a 25% reduction in proliferation of both DN4 and DP thymocytes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• double-positive thymocytes from mutant mice undergo enhanced apoptosis by TCR-stimulation
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• the average numbers of total thymocytes were reduced by half
• the number of cells at the double-negative stage was not different
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• 4- to 6-fold fewer CD4 and CD8 single-positive cells compared to control
• in 3-4 weeks old mutant mice, there were 7- to 9-fold fewer peripheral CD4+ and CD8+ T cells
• in 8-9 weeks old mutant mice, T cell numbers were more similar
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• double-positive thymocytes from mutant mice undergo enhanced apoptosis by TCR-stimulation
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• the average numbers of total thymocytes were reduced by half
• the number of cells at the double-negative stage was not different
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• 4- to 6-fold fewer CD4 and CD8 single-positive cells compared to control
• in 3-4 weeks old mutant mice, there were 7- to 9-fold fewer peripheral CD4+ and CD8+ T cells
• in 8-9 weeks old mutant mice, T cell numbers were more similar
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• double-positive thymocytes from mutant mice undergo enhanced apoptosis by TCR-stimulation
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• the average numbers of total thymocytes were reduced by half
• the number of cells at the double-negative stage was not different
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced numbers of total thymocytes
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• in an in vitro assay, mutant thymocytes underwent OCA peptide 257-264 dependent cell death more readily than control, indicating enhanced negative selection
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• lower proportions of double-positive and single-positive cells, and reduced CD8 SP cell in the peripheral T cell population, both indicating impaired positive selection
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• reduced numbers of total thymocytes
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• in an in vitro assay, mutant thymocytes underwent OCA peptide 257-264 dependent cell death more readily than control, indicating enhanced negative selection
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• lower proportions of double-positive and single-positive cells, and reduced CD8 SP cell in the peripheral T cell population, both indicating impaired positive selection
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• reduced numbers of total thymocytes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 2 fold decrease in total number
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• slightly increased levels of the Th-2 cytokine IL-4 are produced when nave T cells are activated in vitro
• a small subset of T cells produce both IL-4 and IFN-gamma when nave T cells are cultured under Th1 polarizing conditions
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• very few CD8-positive T cells are found in the thymus
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• increase in DP T cell due to reduced ability of T cell precursors to mature past double positive stage
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• 2 fold decrease in total number
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• slightly increased levels of the Th-2 cytokine IL-4 are produced when nave T cells are activated in vitro
• a small subset of T cells produce both IL-4 and IFN-gamma when nave T cells are cultured under Th1 polarizing conditions
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• very few CD8-positive T cells are found in the thymus
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• increase in DP T cell due to reduced ability of T cell precursors to mature past double positive stage
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• six fold less cells as a result of arrested T cell development
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• developing T cells fail to make the transition between DN3 to DN4 stag
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• resulting from arrested T cell development
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• developing T cells fail to make the transition between DN3 to DN4 stage
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• six fold less cells as a result of arrested T cell development
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• developing T cells fail to make the transition between DN3 to DN4 stag
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• resulting from arrested T cell development
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• developing T cells fail to make the transition between DN3 to DN4 stage
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• six fold less cells as a result of arrested T cell development
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• double negative thymocytes of all stages have higher rates of apoptosis
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• thymus cellularity is reduced by about 20-fold
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• the percentage of double negative T cells in the thymus is 85.4% compared to 2.7% in wild-type mice
• there is a significant reduction in proliferating DN4 cells suggesting a partial development block in transitioning to the DP stage
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• the percentage of double positive T cells in the thymus is reduced to 1.8% compared to 84.6% in wild-type mice
• the actual number of DP T cells is 50-fold less than is found in wild-type thymuses
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• developing thymocytes are almost completely blocked at the DN4 to DP transition
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• double negative thymocytes of all stages have higher rates of apoptosis
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• thymus cellularity is reduced by about 20-fold
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• the percentage of double negative T cells in the thymus is 85.4% compared to 2.7% in wild-type mice
• there is a significant reduction in proliferating DN4 cells suggesting a partial development block in transitioning to the DP stage
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• the percentage of double positive T cells in the thymus is reduced to 1.8% compared to 84.6% in wild-type mice
• the actual number of DP T cells is 50-fold less than is found in wild-type thymuses
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• developing thymocytes are almost completely blocked at the DN4 to DP transition
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• double negative thymocytes of all stages have higher rates of apoptosis
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• thymus cellularity is reduced by about 20-fold
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• an increased percentage of double positive thymocytes are apoptotic (15.9% compared to 2.6%)
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• thymus cellularity is reduced by about 15-fold
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• the percentage of double negative T cells in the thymus is 56.2% compared to 2.7% in wild-type mice
• there is a significant reduction in proliferating DN4 cells suggesting a partial development block in transitioning to the DP stage
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• the percentage of double positive T cells in the thymus is reduced to 25% compared to 84.6% in wild-type mice
• the actual number of DP T cells is 50-fold less than is found in wild-type thymuses
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• developing thymocytes are partially blocked at the DN3 to DN4 stage and the DN4 to the DP stage
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• an increased percentage of double positive thymocytes are apoptotic (15.9% compared to 2.6%)
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• thymus cellularity is reduced by about 15-fold
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• the percentage of double negative T cells in the thymus is 56.2% compared to 2.7% in wild-type mice
• there is a significant reduction in proliferating DN4 cells suggesting a partial development block in transitioning to the DP stage
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• the percentage of double positive T cells in the thymus is reduced to 25% compared to 84.6% in wild-type mice
• the actual number of DP T cells is 50-fold less than is found in wild-type thymuses
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• developing thymocytes are partially blocked at the DN3 to DN4 stage and the DN4 to the DP stage
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• an increased percentage of double positive thymocytes are apoptotic (15.9% compared to 2.6%)
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• thymus cellularity is reduced by about 15-fold
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop double positive lymphomas at increased frequency and decreased latency compared to Fbxw7tm1Kei/Fbxw7tm1Kei Tg(Lck-cre)1Cwi mice
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• at 8 weeks of age 2 mice develop thymic lymphoma
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• at 8 weeks of age 2 mice develop thymic lymphoma
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| N |
• unlike in Fbxw7tm1Kei/Fbxw7tm1Kei Tg(Lck-cre)1Cwi mice, T cells do not arrest in S phase or undergo increased apoptosis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• despite increased double positive T cell production stimulated by anti-CD3epsilon treatment, mice produce fewer double positive T cells compared to similarly treated Rag2tm1Fwa homozygotes
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• despite increased double positive T cell production stimulated by anti-CD3epsilon treatment, mice produce fewer double positive T cells compared to similarly treated Rag2tm1Fwa homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice that develop lymphomas die between 14 and 60 weeks
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• after stimulation with antigen, T cell progression into S phase is inhibited and apoptosis is increased
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• the number and percent of double positive thymocytes is increased compared to in wild-type mice due to increased proliferation of double positive thymocytes
• however, the number and proliferation of double negative, CD4+ single positive and CD8+ single positive thymocytes are normal
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• the number of single positive T cells is decreased in peripheral organs such as the spleen and lymph nodes
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• the number of single positive T cells is decreased in peripheral organs such as the spleen and lymph nodes
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• T cells fail to proliferate in response to anti-CD3 or the combination of phorbol 12,13-dibutyrate and ionomycin
• after stimulation with antigen, T cell progression into S phase is inhibited and apoptosis is increased
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• 12 of 23 mice develop aggressive lymphomas with massive thymic enlargement due to clonal expansion of double positive thymocytes
• tumors contain uniform populations of immature lymphoid cells with some areas of necrosis
• early and late onset tumors exhibit identical phenotype
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• after stimulation with antigen, T cell progression into S phase is inhibited and apoptosis is increased
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• the number and percent of double positive thymocytes is increased compared to in wild-type mice due to increased proliferation of double positive thymocytes
• however, the number and proliferation of double negative, CD4+ single positive and CD8+ single positive thymocytes are normal
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• the number of single positive T cells is decreased in peripheral organs such as the spleen and lymph nodes
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• the number of single positive T cells is decreased in peripheral organs such as the spleen and lymph nodes
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• T cells fail to proliferate in response to anti-CD3 or the combination of phorbol 12,13-dibutyrate and ionomycin
• after stimulation with antigen, T cell progression into S phase is inhibited and apoptosis is increased
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• after stimulation with antigen, T cell progression into S phase is inhibited and apoptosis is increased
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• T cell development is more severely arrested than in Ctcftm1Laat/Ctcftm1Laat Tg(Lck-cre)1Cwi mice
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• mice exhibit an almost complete lack of mature T cells in the spleen
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• the number of immature single positive cells in the thymus is increased compared to in wild-type mice
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• T cell development is more severely arrested than in Ctcftm1Laat/Ctcftm1Laat Tg(Lck-cre)1Cwi mice
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• mice exhibit an almost complete lack of mature T cells in the spleen
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• the number of immature single positive cells in the thymus is increased compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• modestly
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• the numbers of mature CD4+ and CD8+ cells in the spleen and lymph nodes are reduced compared to in wild-type mice
• however, the ratio of mature single positive cells to double positive cells is normal
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• the numbers of mature CD4+ and CD8+ cells in the spleen and lymph nodes are reduced compared to in wild-type mice
• however, the ratio of mature single positive cells to double positive cells is normal
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• modestly
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• the numbers of mature CD4+ and CD8+ cells in the spleen and lymph nodes are reduced compared to in wild-type mice
• however, the ratio of mature single positive cells to double positive cells is normal
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• the numbers of mature CD4+ and CD8+ cells in the spleen and lymph nodes are reduced compared to in wild-type mice
• however, the ratio of mature single positive cells to double positive cells is normal
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• modestly
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cells at the DN3L to immature single positive stage are smaller than in wild-type mice while double positive cells are larger than in wild-type mice
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• alpha beta T cell differentiation is defective
• the number of DN3, DN4 and immature single positive cells is increased compared to in wild-type mice
• mice exhibit only a 4-fold increase in thymocytes during the transition from immature single positive to double positive T cells compared to a 90-fold increase in wild-type mice
• however, sigma delta T cell differentiation and TCR rearrangement are normal
• mice exhibit a defect in the transition from immature single positive cells to double positive cells
• the number of immature single positive T cells undergoing cell cycling is half as many as in wild-type mice
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• the number of double negative DN3 and DN4 cells is increased compared to in wild-type mice
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• the numbers of mature CD4+ and CD8+ cells in the spleen and lymph nodes are reduced compared to in wild-type mice
• however, the ratio of mature single positive cells to double positive cells is normal
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• the numbers of mature CD4+ and CD8+ cells in the spleen and lymph nodes are reduced compared to in wild-type mice
• however, the ratio of mature single positive cells to double positive cells is normal
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• the number of mature single positive T cells is decreased compared to in wild-type mice
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• the number of immature single positive cells in the thymus is increased compared to in wild-type mice
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• cells at the DN3L to immature single positive stage are smaller than in wild-type mice while double positive cells are larger than in wild-type mice
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• alpha beta T cell differentiation is defective
• the number of DN3, DN4 and immature single positive cells is increased compared to in wild-type mice
• mice exhibit only a 4-fold increase in thymocytes during the transition from immature single positive to double positive T cells compared to a 90-fold increase in wild-type mice
• however, sigma delta T cell differentiation and TCR rearrangement are normal
• mice exhibit a defect in the transition from immature single positive cells to double positive cells
• the number of immature single positive T cells undergoing cell cycling is half as many as in wild-type mice
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• the number of double negative DN3 and DN4 cells is increased compared to in wild-type mice
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• the numbers of mature CD4+ and CD8+ cells in the spleen and lymph nodes are reduced compared to in wild-type mice
• however, the ratio of mature single positive cells to double positive cells is normal
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• the numbers of mature CD4+ and CD8+ cells in the spleen and lymph nodes are reduced compared to in wild-type mice
• however, the ratio of mature single positive cells to double positive cells is normal
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• the number of mature single positive T cells is decreased compared to in wild-type mice
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• the number of immature single positive cells in the thymus is increased compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the number of HSAhiCD69+ and
HSAhi TCRbetahi positively selected thymocytes are approximately 20% of those in littermate control or Zbtb7b-deficient mice
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• absolute numbers of CD4+ single positive mature thymocytes are reduced between 5-10 fold compared to controls
• however, the percentage of CD4+ T cells in peripheral lymph nodes is only slightly reduced
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• the number of HSAhiCD69+ and
HSAhi TCRbetahi positively selected thymocytes are approximately 20% of those in littermate control or Zbtb7b-deficient mice
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• absolute numbers of CD4+ single positive mature thymocytes are reduced between 5-10 fold compared to controls
• however, the percentage of CD4+ T cells in peripheral lymph nodes is only slightly reduced
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the number of HSAhiCD69+ and
HSAhi TCRbetahi positively selected thymocytes are approximately 20% of those in littermate control or Zbtb7b-deficient mice
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• absolute numbers of CD4+ single positive mature thymocytes are reduced by 5 to 10 fold compared to controls
• however, the percentage of CD4+ T cells in peripheral lymph nodes is only slightly reduced
|
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• the number of HSAhiCD69+ and
HSAhi TCRbetahi positively selected thymocytes are approximately 20% of those in littermate control or Zbtb7b-deficient mice
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• absolute numbers of CD4+ single positive mature thymocytes are reduced by 5 to 10 fold compared to controls
• however, the percentage of CD4+ T cells in peripheral lymph nodes is only slightly reduced
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the number of HSAhiCD69+ and
HSAhi TCRbetahi positively selected thymocytes are approximately 20% of those in littermate control or Zbtb7b-deficient mice
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• absolute numbers of CD4+ single positive mature thymocytes are reduced by 5 to 10 fold compared to controls
• the percentage of CD4+ T cells in peripheral lymph nodes is reduced by almost 20-fold
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• the number of HSAhiCD69+ and
HSAhi TCRbetahi positively selected thymocytes are approximately 20% of those in littermate control or Zbtb7b-deficient mice
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• absolute numbers of CD4+ single positive mature thymocytes are reduced by 5 to 10 fold compared to controls
• the percentage of CD4+ T cells in peripheral lymph nodes is reduced by almost 20-fold
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• immature T cell lymphomas develop with shorter latency than in Ightm1(PAX5)Mbu homozygotes
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• immature T cell lymphomas develop with shorter latency than in Ightm1(PAX5)Mbu homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cell development is more severely arrested than in Ctcftm1Laat/Ctcftm1Laat Tg(Lck-cre)1Cwi mice
• mice exhibit a severe block to T cell development at the immature single positive stage
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• mice exhibit a almost complete lack of double positive cells in the thymus
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• strongly reduced in the spleen
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• strongly reduced in the spleen
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• T cell development is more severely arrested than in Ctcftm1Laat/Ctcftm1Laat Tg(Lck-cre)1Cwi mice
• mice exhibit a severe block to T cell development at the immature single positive stage
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• mice exhibit a almost complete lack of double positive cells in the thymus
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• strongly reduced in the spleen
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• strongly reduced in the spleen
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not exhibit an osteopetrotic phenotype unlike null mice
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• thymus cellularity is reduced about 97%
|
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• the absolute number of double negative cells is decreased about 40% however the proportion of double negative cells is increased to about 60% of total thymocytes
• about 90% of the double negative cells are CD44-CD25+ DN3 cells
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• the absolute number of double positive cells is greatly decreased
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• a block in thymocyte maturation at the DN3 stage or in the transition from DN3 to DN4 appears to occur
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• the absolute number of CD4 single positive cells is greatly decreased
|
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• the absolute number of CD8 single positive cells is greatly decreased
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• the number of gamma delta TCR bearing thymocytes is decreased
|
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• thymus cellularity is reduced about 97%
|
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• the absolute number of double negative cells is decreased about 40% however the proportion of double negative cells is increased to about 60% of total thymocytes
• about 90% of the double negative cells are CD44-CD25+ DN3 cells
|
|
• the absolute number of double positive cells is greatly decreased
|
|
• a block in thymocyte maturation at the DN3 stage or in the transition from DN3 to DN4 appears to occur
|
|
• the absolute number of CD4 single positive cells is greatly decreased
|
|
• the absolute number of CD8 single positive cells is greatly decreased
|
|
• the number of gamma delta TCR bearing thymocytes is decreased
|
|
• thymus cellularity is reduced about 97%
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• 10-fold
|
|
|
• mice exhibit a disproportionate increased (2-fold) in DN3 thymocytes compared to in wild-type mice
|
|
|
• alpha beta T cell development is incompletely blocked at the DN3 stage unlike in wild-type mice
• however, delta gamma T cell development and pre-TCR signaling are normal
|
|
|
• 10-fold
|
|
|
• mice exhibit a disproportionate increased (2-fold) in DN3 thymocytes compared to in wild-type mice
|
|
|
• alpha beta T cell development is incompletely blocked at the DN3 stage unlike in wild-type mice
• however, delta gamma T cell development and pre-TCR signaling are normal
|
|
|
• 10-fold
|
|
|
• mice exhibit a disproportionate increased (2-fold) in DN3 thymocytes compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• thymus size normal
• thymocyte number normal
• no increase in apoptosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• completely resistant to apoptosis
|
|
• completely resistant to apoptosis
|
|
• completely resistant to apoptosis
|
|
• completely resistant to apoptosis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 |
• thymocyte numbers are reduced about 60% however peripheral T cell numbers are normal
|
|
|
• thymocyte numbers are reduced about 60% however peripheral T cell numbers are normal
|
|
|
• thymocyte numbers are reduced about 60% however peripheral T cell numbers are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• the thymus is depleted of developing T cells and the residual cells are relatively enriched with immature thymocytes
• no peripheral T cells are seen
|
|
|
• the thymus is depleted of developing T cells and the residual cells are relatively enriched with immature thymocytes
• no peripheral T cells are seen
|
|
|
• the thymus is depleted of developing T cells and the residual cells are relatively enriched with immature thymocytes
• no peripheral T cells are seen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• progressive decrease in cycling T cells is observed from second to third cell division in vitro, along with large number of nonblast T cells that appear to fail to enter cell cycle
|
|
• a 5- to 7-fold decrease in proliferation is observed relative to wild-type cells in vitro after 48 hours of TCR/CD3 stimulation; fewer mutant cells are in S phase
|
|
• a 5- to 7-fold decrease in proliferation is observed relative to wild-type cells in vitro after 48 hours of TCR/CD3 stimulation; fewer mutant cells are in S phase
|
|
• a 5- to 7-fold decrease in proliferation is observed relative to wild-type cells in vitro after 48 hours of TCR/CD3 stimulation; fewer mutant cells are in S phase
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normally differentiating T, B, and myeloid cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• half as many CD4+ T cells undergo apoptosis compared to in wild-type mice
|
|
• proliferation of single positive thymocytes stimulated with anti-CD3 and anti-CD3 plus anti-CD28 is almost half as much as in similarly treated wild-type cells
|
|
• CD4+ T cell thymocytes are increased compared to in wild-type mice
|
|
• CD8+ T cell thymocytes are increased compared to in wild-type mice
|
|
• spleen and lymph nodes have half as many T cells as in wild-type mice
|
|
• the percent of double positive thymocytes is slightly lower percent than in wild-type mice
|
|
• the percentage of CD8+ T cells is decreased compared to in wild-type mice
|
|
• the ratio of CD4+ to CD8+ peripheral T cells is skewed in favor of CD4+ T cells unlike in wild-type mice
|
|
• with less than half of T cells
|
|
• with less than half of T cells
|
|
• half as many CD4+ T cells undergo apoptosis compared to in wild-type mice
|
|
• proliferation of single positive thymocytes stimulated with anti-CD3 and anti-CD3 plus anti-CD28 is almost half as much as in similarly treated wild-type cells
|
|
• CD4+ T cell thymocytes are increased compared to in wild-type mice
|
|
• CD8+ T cell thymocytes are increased compared to in wild-type mice
|
|
• spleen and lymph nodes have half as many T cells as in wild-type mice
|
|
• the percent of double positive thymocytes is slightly lower percent than in wild-type mice
|
|
• the percentage of CD8+ T cells is decreased compared to in wild-type mice
|
|
• the ratio of CD4+ to CD8+ peripheral T cells is skewed in favor of CD4+ T cells unlike in wild-type mice
|
|
• with less than half of T cells
|
|
• half as many CD4+ T cells undergo apoptosis compared to in wild-type mice
|
|
• proliferation of single positive thymocytes stimulated with anti-CD3 and anti-CD3 plus anti-CD28 is almost half as much as in similarly treated wild-type cells
|
|
• half as many CD4+ T cells undergo apoptosis compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• anti-Fas antibody fails to induce cell death in T-cells as it does in controls
• resistant to FasL induced cell death
|
| N |
• thymus, spleen, and lymph nodes all appear to be normal
|
|
• peripheral B-cells are increased in number
|
|
• TCR activation of T-cells is reduced
|
|
• both CD4+ and CD8+ peripheral T-cells are reduced in number
• peripheral T-cells divide less efficiently when transplanted to Rag1 deficient mice
|
|
• peripheral B-cells are increased in number
|
|
• TCR activation of T-cells is reduced
|
|
• both CD4+ and CD8+ peripheral T-cells are reduced in number
• peripheral T-cells divide less efficiently when transplanted to Rag1 deficient mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all die of tumors by 50 weeks of age
|
|
• unlike in thymocyte conditional null mice (carrying Trp53tm1Brd and Tg(Lck-cre)1Cwi ), about 40% of tumors are metastatic
|
|
• predominantly peripheral and thymic lymphomas by 50 weeks of age
|
|
• by 50 weeks of age
|
|
• by 50 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the T cell defect seen in germline null mice is recapitulated in these mice
• however, all lymph nodes are present
|
|
• the T cell defect seen in germline null mice is recapitulated in these mice
• however, all lymph nodes are present
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• most mice develop signs of colitis by 2 months of age with elongation of crypts and mucosal thickening
|
|
|
• unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation
• spreading of TCRhigh CD4 or CD8 SP thymocytes on a surface covered with antibodies to CD3 and CD28 is reduced
• migratory responses to CCL19 or CXCL12 are reduced even more than in Wastm1Sbs homozygotes and compared to in wild-type cells
|
|
|
• mice exhibit a reduction in large and cycling double negative 3 (DN3) cells and, to a lesser degree, DN4 cells
• the ratio of DN3 to DN4 is skewed (3.18+/-1.89 compared to 0.74+/-0.45 in wild-type mice and 1.49+/-0.90 in Wastm1Sbs homozygotes)
|
|
|
• the percent of double positive (DP) CD69hi cells is greater than in wild-type
|
|
|
• the numbers of CD4+ and CD8+ T lymphocytes is reduced
|
|
|
• the number of thymocytes is reduced
• however, there is no increase in apoptosis
|
|
|
• mice have fewer single positive CD69hi cells compared to in wild-type mice and Wastm1Sbs homozygotes
|
|
|
• the number of single positive CD69low CD62Llow cells is increased compared to in wild-type mice
|
|
|
• unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation
• spreading of TCRhigh CD4 or CD8 SP thymocytes on a surface covered with antibodies to CD3 and CD28 is reduced
• migratory responses to CCL19 or CXCL12 are reduced even more than in Wastm1Sbs homozygotes and compared to in wild-type cells
|
|
|
• mice exhibit a reduction in large and cycling double negative 3 (DN3) cells and, to a lesser degree, DN4 cells
• the ratio of DN3 to DN4 is skewed (3.18+/-1.89 compared to 0.74+/-0.45 in wild-type mice and 1.49+/-0.90 in Wastm1Sbs homozygotes)
|
|
|
• the percent of double positive (DP) CD69hi cells is greater than in wild-type
|
|
|
• the numbers of CD4+ and CD8+ T lymphocytes is reduced
|
|
|
• the number of thymocytes is reduced
• however, there is no increase in apoptosis
|
|
|
• mice have fewer single positive CD69hi cells compared to in wild-type mice and Wastm1Sbs homozygotes
|
|
|
• the number of single positive CD69low CD62Llow cells is increased compared to in wild-type mice
|
|
|
• most mice develop signs of colitis by 2 months of age with elongation of crypts and mucosal thickening
|
|
|
• most mice develop signs of colitis by 2 months of age with elongation of crypts and mucosal thickening
|
|
|
• most mice develop signs of colitis by 2 months of age with elongation of crypts and mucosal thickening
|
|
|
• the number of thymocytes is reduced
• however, there is no increase in apoptosis
|
|
|
• unlike wild-type thymocytes, single positive (SP) thymocytes fail to proliferate after CD3 stimulation
• spreading of TCRhigh CD4 or CD8 SP thymocytes on a surface covered with antibodies to CD3 and CD28 is reduced
• migratory responses to CCL19 or CXCL12 are reduced even more than in Wastm1Sbs homozygotes and compared to in wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal myeloid, T lymphoid and B lymphoid lineages and cell cycle of lineage progenitors
|
| N |
• mice exhibit normal myeloid, T lymphoid and B lymphoid lineages and cell cycle of lineage progenitors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• general decrease in cellularity is observed
|
|
• specific reduction in CD4+CD8- and CD4-CD8+ single positive (SP) thymocytes is found
|
|
• general decrease in cellularity is observed
|
|
• specific reduction in CD4+CD8- and CD4-CD8+ single positive (SP) thymocytes is found
|
|
• general decrease in cellularity is observed
|
|
• specific reduction in CD4+CD8- and CD4-CD8+ single positive (SP) thymocytes is found
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 1/8 to 1/10 as many thymocytes as in controls
|
|
• higher levels of apoptosis in DN3, DN4, and DP cells
|
|
• 50% of thymocytes with a double negative phenotype
|
|
• T cell development is blocked at the DN4 stage
|
|
• total mononuclear cell preparations from the intestine shows at least a 9-fold higher frequency of mast cell progenitors than wild-type mice
• treatment of mice with anti-TNFalpha antibody lowers the numbers of mast cell progenitors in the intestine
|
|
• 10-fold increase in serum TNFalpha levels by 4 months of age but declines to 3-fold increase in late-stage polyposis
|
|
• 1/8 to 1/10 as many thymocytes as in controls
|
|
• higher levels of apoptosis in DN3, DN4, and DP cells
|
|
• 50% of thymocytes with a double negative phenotype
|
|
• T cell development is blocked at the DN4 stage
|
|
• total mononuclear cell preparations from the intestine shows at least a 9-fold higher frequency of mast cell progenitors than wild-type mice
• treatment of mice with anti-TNFalpha antibody lowers the numbers of mast cell progenitors in the intestine
|
|
• 1/8 to 1/10 as many thymocytes as in controls
|
|
• dysplastic crypts with hyperchromatic nuclei, expanding at the luminal surface of the mucosa, neighboring well spaced, nondysplastic crypts and villi
|
|
• intestinal lesions are seen as early as 2 months after birth and mice develop adenomatous polyps that are typically infiltrated with intraepithelial mast cells restricted to the lesions
• mice treated with anti-TNFalpha antibody every 2 days for 2 weeks show fewer polyps than controls and the polyps that persist have a more flattened and differentiated morphology and are smaller, and the mean vessel volume in the polyps is 4-times less than in untreated mice
|
|
• mice show adenomas in the small and large intestine from 2 months of age which typically have a tubovillous appearance
• adenomas are devoid of differentiated cells
|
|
• 10-fold increase in serum TNFalpha levels by 4 months of age but declines to 3-fold increase in late-stage polyposis
|
|
• mice show adenomas in the small and large intestine from 2 months of age which typically have a tubovillous appearance
• adenomas are devoid of differentiated cells
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| familial adenomatous polyposis | DOID:0050424 |
OMIM:PS175100 |
J:128606 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double positive (DP) thymocytes cannot progress to the single positive (SP)
• DP thymocytes show defects in induction of TCRb, CD69, and CD5 which are markers of positive selection
• negative selection was unaffected
|
|
• decreased numbers of T lymphocytes compared to controls
|
|
• double positive (DP) thymocytes cannot progress to the single positive (SP)
• DP thymocytes show defects in induction of TCRb, CD69, and CD5 which are markers of positive selection
• negative selection was unaffected
|
|
• decreased numbers of T lymphocytes compared to controls
|
|
• decreased numbers of T lymphocytes compared to controls
|
|
• ERK activation is defective in Ppp3r1-deficient animals
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cell lymphoblastic leukemia/lymphoma in 8 of 15 mice
|
|
• T cell lymphoblastic leukemia/lymphoma in 8 of 15 mice
|
|
• T cell lymphoblastic leukemia/lymphoma in 8 of 15 mice
|
| N |
• T and B cell development is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice die at an average of 15 weeks
|
|
• in diseased mice
|
|
• 5-fold reduction in cellularity in neonates
|
|
• in diseased mice
|
|
• in the percentage but not the absolute numbers
|
|
• increase in CD4low/CD8high cells at 6 to 8 weeks
|
|
• block at the double negative to double positive transition
|
|
• 4-fold increase in the percent of immature single positive cells at 6 to 8 weeks
|
|
• in 1 of 8 mice
|
|
• in moribund mice
|
|
• in moribund mice
|
|
• in diseased mice
|
|
• in moribund mice
|
|
• in diseased mice
|
|
• 5-fold reduction in cellularity in neonates
|
|
• in diseased mice
|
|
• in the percentage but not the absolute numbers
|
|
• increase in CD4low/CD8high cells at 6 to 8 weeks
|
|
• block at the double negative to double positive transition
|
|
• 4-fold increase in the percent of immature single positive cells at 6 to 8 weeks
|
|
• in diseased mice
|
|
• 5-fold reduction in cellularity in neonates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all mice die at an average of 15 weeks
|
|
• in neonates and at 6 weeks
|
|
• in the thymus and spleen
|
|
• effacement of medullary and cortical substructures in diseased thymus
|
|
• massively in diseased mice due to overpopulation with immature and double positive T cells
|
|
• 2-fold reduction in mature TCRbetahigh/CD5high thymocytes at 10 to 14 days
|
|
• 3-fold increase immature TCRbetaint/CD5low thymocytes at 10 to 14 days
|
|
• massively in diseased mice due to overpopulation with immature and double positive T cells
|
|
• 2.6-fold reduction at 10 to 14 days
|
|
• increase in CD4low/CD8high cells at 6 to 8 weeks
• 10-fold increase in absolute number of CD4low/CD8high cells at 10 to 14 days
|
|
• block at the double negative to double positive transition
• defects in positive selection and CD4 lineage commitment
|
|
• 4-fold increase in the percent of immature single positive cells at 6 to 8 weeks
|
|
• with general hyperproliferation of immature T cells and infiltration into nonlymphatic organs (lung, liver and kidney)
|
|
• in moribund mice
|
|
• in moribund mice
|
|
• massively in diseased mice due to overpopulation with immature and double positive T cells
|
|
• in moribund mice
|
|
• in tumor cells
|
|
• in neonates and at 6 weeks
|
|
• in the thymus and spleen
|
|
• in tumorigenic T cells
|
|
• in neonates and at 6 weeks
|
|
• in the thymus and spleen
|
|
• effacement of medullary and cortical substructures in diseased thymus
|
|
• massively in diseased mice due to overpopulation with immature and double positive T cells
|
|
• 2-fold reduction in mature TCRbetahigh/CD5high thymocytes at 10 to 14 days
|
|
• 3-fold increase immature TCRbetaint/CD5low thymocytes at 10 to 14 days
|
|
• massively in diseased mice due to overpopulation with immature and double positive T cells
|
|
• 2.6-fold reduction at 10 to 14 days
|
|
• increase in CD4low/CD8high cells at 6 to 8 weeks
• 10-fold increase in absolute number of CD4low/CD8high cells at 10 to 14 days
|
|
• block at the double negative to double positive transition
• defects in positive selection and CD4 lineage commitment
|
|
• 4-fold increase in the percent of immature single positive cells at 6 to 8 weeks
|
|
• in neonates and at 6 weeks
|
|
• effacement of medullary and cortical substructures in diseased thymus
|
|
• massively in diseased mice due to overpopulation with immature and double positive T cells
|
|
• 2-fold reduction in mature TCRbetahigh/CD5high thymocytes at 10 to 14 days
|
|
• 3-fold increase immature TCRbetaint/CD5low thymocytes at 10 to 14 days
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal numbers of double negative, double positive, CD4 single positive and CD8 single positive T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal numbers of double negative, double positive, CD4 single positive and CD8 single positive T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal numbers of double negative, double positive, CD4 single positive and CD8 single positive T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all die of thymic lymphomas by 50 weeks of age
|
|
• in all mice by 50 weeks of age
|
|
• in all mice by 50 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 40-100 fold reduction in cell numbers in the thymus
|
|
• absence of double positive T cells
|
|
• T cells become arrested when cre inactivation occurs primarily at DN4 stage but sometimes earlier
• leads to expression of CD4 and to death of T cells
|
|
• very small numbers of CD4+ cells
|
|
• absence of CD8+ cells
|
|
• 40-100 fold reduction in cell numbers in the thymus
|
|
• absence of double positive T cells
|
|
• T cells become arrested when cre inactivation occurs primarily at DN4 stage but sometimes earlier
• leads to expression of CD4 and to death of T cells
|
|
• very small numbers of CD4+ cells
|
|
• absence of CD8+ cells
|
|
• 40-100 fold reduction in cell numbers in the thymus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cells arrested in G1 phase of cell cycle leading to a 10 fold increase in cell numbers as opposed to animals lacking TgN(LCKprBCL2)36Sjk
|
|
• cells arrested in G1 phase of cell cycle leading to a 10 fold increase in cell numbers as opposed to animals lacking TgN(LCKprBCL2)36Sjk
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• marked reduction in both proliferation and differentiation into DP cells on a per cell basis
|
|
• marked reduction in both proliferation and differentiation into DP cells on a per cell basis
|
|
• marked reduction in both proliferation and differentiation into DP cells on a per cell basis
|
|
• marked reduction in both proliferation and differentiation into DP cells on a per cell basis
|
|
• marked reduction in both proliferation and differentiation into DP cells on a per cell basis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thymic cellularity reduced to 1/8 normal
|
|
• most thymocytes are double negative
• a lower percentage of double negative stage 4 cells (DN4) and increase in DN3 cells
|
|
• only moderate reductions in mature T cells in spleen and lymph nodes
|
|
• absolute numbers of double positive cells reduced
|
|
• thymic cellularity reduced to 1/8 normal
|
|
• most thymocytes are double negative
• a lower percentage of double negative stage 4 cells (DN4) and increase in DN3 cells
|
|
• only moderate reductions in mature T cells in spleen and lymph nodes
|
|
• absolute numbers of double positive cells reduced
|
|
• lymph nodes reduced 50%
|
|
• thymic cellularity reduced to 1/8 normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 50% of mice develop T cell lymphomas later in life
|
|
• 50% of mice develop T cell lymphomas later in life
|
| N |
• the numbers of double negative cells are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thymocytes display normal or slightly enhanced proliferation in vivo
|
|
• some mice have very small thymuses (13 x 106 cells) with few DN4 cells, but some have larger thymuses (115 x 106 cells)
|
|
• total thymocyte number is decreased >3-fold compared to wild-type
|
|
• mice have a substantial population of double-positive T cells
|
|
• thymocytes display normal or slightly enhanced proliferation in vivo
|
|
• some mice have very small thymuses (13 x 106 cells) with few DN4 cells, but some have larger thymuses (115 x 106 cells)
|
|
• total thymocyte number is decreased >3-fold compared to wild-type
|
|
• mice have a substantial population of double-positive T cells
|
|
• some mice have very small thymuses (13 x 106 cells) with few DN4 cells, but some have larger thymuses (115 x 106 cells)
|
|
• total thymocyte number is decreased >3-fold compared to wild-type
|
|
• thymocytes display normal or slightly enhanced proliferation in vivo
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased apoptosis at double negative T cell stage
|
|
• block at the double-negative stage between DN2 and DN3
|
|
• decreased number of peripheral T cells
• detected peripheral T cells did not undergo cre-mediated recombination
|
|
• reduction of the total number of thymocytes
|
|
• reduction of double-negative cells in DN3 and DN4 subsets, but not in DN1 or DN2 subsets
|
|
• increased apoptosis at double negative T cell stage
|
|
• block at the double-negative stage between DN2 and DN3
|
|
• decreased number of peripheral T cells
• detected peripheral T cells did not undergo cre-mediated recombination
|
|
• reduction of the total number of thymocytes
|
|
• reduction of double-negative cells in DN3 and DN4 subsets, but not in DN1 or DN2 subsets
|
|
• increased apoptosis at double negative T cell stage
|
|
• reduction of the total number of thymocytes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• two fold reduction of thymocytes although the developmental profile seems normal
|
|
• two fold reduction of thymocytes although the developmental profile seems normal
|
|
• two fold reduction of thymocytes although the developmental profile seems normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• BAK from T cells is more sensitive to apoptotic signals
• earlier translocation of cytochrome c out of mitochondria
• earlier caspase activation
• thymocytes cultured with antibody to CD3 die more rapidly
|
|
• further shrinkage of thymus when mice injected with antibody to CD3
|
|
• two fold reduction of thymocytes although the developmental profile seems normal
• 90% of double+ thymocytes killed when mice injected with antibody to CD3
|
|
• BAK from T cells is more sensitive to apoptotic signals
• earlier translocation of cytochrome c out of mitochondria
• earlier caspase activation
• thymocytes cultured with antibody to CD3 die more rapidly
|
|
• BAK from T cells is more sensitive to apoptotic signals
• earlier translocation of cytochrome c out of mitochondria
• earlier caspase activation
• thymocytes cultured with antibody to CD3 die more rapidly
|
|
• further shrinkage of thymus when mice injected with antibody to CD3
|
|
• two fold reduction of thymocytes although the developmental profile seems normal
• 90% of double+ thymocytes killed when mice injected with antibody to CD3
|
|
• BAK from T cells is more sensitive to apoptotic signals
• earlier translocation of cytochrome c out of mitochondria
• earlier caspase activation
• thymocytes cultured with antibody to CD3 die more rapidly
|
|
• further shrinkage of thymus when mice injected with antibody to CD3
|
|
• two fold reduction of thymocytes although the developmental profile seems normal
• 90% of double+ thymocytes killed when mice injected with antibody to CD3
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• fewer than the expected numbers (6.5% vs 12.5%) of mutants are born, indicating partial prenatal lethality; time of lethality not determined
|
|
• those double negative (DN) 3 cells that are able to develop into DN4 cells, exhibit increased apoptosis compared to controls
|
|
• decrease in total thymocyte number at 4-6 weeks of age
• 10-fold reduction in the number of alpha/beta TCR+ thymocytes
|
|
• double negative (DN) thymocytes fail to develop into large active double positive thymocytes
• accumulation of cells in the CD44-CD25+ DN3 stage and decreased CD44-CD25- DN4 cells, indicating a partial arrest at the DN3 to DN4 transition
|
|
• reduction in the CD4/CD8 ratio (1.33 vs 3-4 in controls)
|
|
• variable numbers of total SP CD8 cell numbers, with a decrease in most cases but increases in other cases
|
|
• those double negative (DN) 3 cells that are able to develop into DN4 cells, exhibit increased apoptosis compared to controls
|
|
• decrease in total thymocyte number at 4-6 weeks of age
• 10-fold reduction in the number of alpha/beta TCR+ thymocytes
|
|
• double negative (DN) thymocytes fail to develop into large active double positive thymocytes
• accumulation of cells in the CD44-CD25+ DN3 stage and decreased CD44-CD25- DN4 cells, indicating a partial arrest at the DN3 to DN4 transition
|
|
• reduction in the CD4/CD8 ratio (1.33 vs 3-4 in controls)
|
|
• variable numbers of total SP CD8 cell numbers, with a decrease in most cases but increases in other cases
|
|
• those double negative (DN) 3 cells that are able to develop into DN4 cells, exhibit increased apoptosis compared to controls
|
|
• decrease in total thymocyte number at 4-6 weeks of age
• 10-fold reduction in the number of alpha/beta TCR+ thymocytes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 10-fold reduction
|
|
• partial arrest at the double negative 3 (DN3) to double negative 4 (DN4) transition
• partial impairment in generation of double positive cells
|
|
• 10-fold reduction
|
|
• 10-fold reduction
|
|
• partial impairment in generation of double positive cells
• partial arrest at the double negative 3 (DN3) to double negative 4 (DN4) transition
|
|
• 10-fold reduction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice have some delay in recovering from an influenza infection compared to controls
• mice show pronounced lymphocytic accumulation in the tertiary lymphoid tissue after influenza infection compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• the number of NK T cells is decreased 90% compared to in wild-type mice
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
• the number of NK T cells is decreased 90% compared to in wild-type mice
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
• in most mice following immunization with TNP-CGG
• however, some mice could mount a partial antibody response
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• very small
|
|
• double negative thymocytes exhibit impaired proliferation
|
|
• mice exhibit defects in the transition from double negative to double positive thymocytes
|
|
• slightly in the thymus
|
|
• in the thymus
|
|
• in the thymus and spleen
|
|
• in the thymus and spleen
|
|
• very small
|
|
• double negative thymocytes exhibit impaired proliferation
|
|
• mice exhibit defects in the transition from double negative to double positive thymocytes
|
|
• slightly in the thymus
|
|
• in the thymus
|
|
• in the thymus and spleen
|
|
• in the thymus and spleen
|
|
• very small
|
|
• double negative thymocytes exhibit impaired proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Mapk1 protein levels are decreased ~3-fold at the DN3 stage and from 25-100-fold at the DN4 stage
|
|
• there is a substantial increase in number of DN3 thymocytes over DN4, consistent with partial block in maturation
|
|
• there is a larger decrease in CD4 T cells than CD8 T cells; ratio of CD4:CD8 goes down to 2.2 from 3.2 in wild-type
|
|
• there is a decrease in CD8 T cells; ratio of CD4:CD8 goes down to 2.2 from 3.2 in wild-type
|
|
• there is a substantial increase in number of DN3 thymocytes over DN4, consistent with partial block in maturation
|
|
• there is a larger decrease in CD4 T cells than CD8 T cells; ratio of CD4:CD8 goes down to 2.2 from 3.2 in wild-type
|
|
• there is a decrease in CD8 T cells; ratio of CD4:CD8 goes down to 2.2 from 3.2 in wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thymocytes display normal or slightly enhanced proliferation in vivo
|
|
• total number of double-positive (DP) thymocytes is reduced by 30%
|
|
• there is a substantial increase in number of DN3 thymocytes over DN4, consistent with partial block in maturation
|
|
• thymocytes display normal or slightly enhanced proliferation in vivo
|
|
• total number of double-positive (DP) thymocytes is reduced by 30%
|
|
• there is a substantial increase in number of DN3 thymocytes over DN4, consistent with partial block in maturation
|
|
• thymocytes display normal or slightly enhanced proliferation in vivo
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• in 2 week old mice that are not injected with MOG peptide, T cell development is normal
• the fraction of absolute numbers of CD4+ and CD8+ T cells in spleen and lymph nodes is similar to controls
• percentages and numbers of thymic compartment subsets in 4-6 week old mice are similar to controls
|
|
• reduced disease severity is observed in mice injected with MOG35-55 peptide as compared to MOG-injected wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• unusually high percentage of thymocytes expressed TCR gamma-delta and gamma-delta cells were prevalent in the double negative compartment and decreased numbers of alpha-beta T cells
|
|
• decreased numbers of alpha-beta T cells
|
|
• cell numbers in thymi were reduced nearly 10-fold relative to controls, however there were normal numbers of double negative cells in thym
• increased percentage (43% versus 11% of wildtype at 6 hours and 68% versus 30% at 24 hours) of dying thymocytes when grown in vitro
|
|
• unusually high percentage of thymocytes expressed TCR gamma-delta and gamma-delta cells were prevalent in the double negative compartment and decreased numbers of alpha-beta T cells
|
|
• decreased numbers of alpha-beta T cells
|
|
• cell numbers in thymi were reduced nearly 10-fold relative to controls, however there were normal numbers of double negative cells in thym
• increased percentage (43% versus 11% of wildtype at 6 hours and 68% versus 30% at 24 hours) of dying thymocytes when grown in vitro
|
|
• cell numbers in thymi were reduced nearly 10-fold relative to controls, however there were normal numbers of double negative cells in thym
• increased percentage (43% versus 11% of wildtype at 6 hours and 68% versus 30% at 24 hours) of dying thymocytes when grown in vitro
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• moderate in the thymus
• however, numbers are normal in the blood, thymus and spleen
|
|
• less so than in conditional Nmt1tm1.1Poru and Nmt2tm1.1Poru knock-out mice
|
|
• CD4+ and CD8+ single positive cells
|
|
• moderate in the thymus
• however, numbers are normal in the blood, thymus and spleen
|
|
• less so than in conditional Nmt1tm1.1Poru and Nmt2tm1.1Poru knock-out mice
|
|
• CD4+ and CD8+ single positive cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• positive selection is diminished significantly
|
|
• CD4 to CD8 ratio (% of mature CD4 and CD8 T cells) is 20 compared to 257 in non transgenic littermates
|
|
• positive selection is diminished significantly
|
|
• CD4 to CD8 ratio (% of mature CD4 and CD8 T cells) is 20 compared to 257 in non transgenic littermates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in vitro, TCR/CD3 stimulation shows a 5-7 fold decrease in proliferating T cells compared to controls, specifically CD8+CD4lo and CD8+ CD4- populations
|
|
• null mice exhibit a consistent reduction in cellularity compared to wild-type or heterozygotes
|
|
• there is an increase in the population of the T cells in the late double negative (DN4) stage in the neonatal thymus
|
|
• percentage of double positive thymocytes is severely reduced
|
|
• CD8+ cells are greatly increased in number
• CD8+ populations in the thymus express TCR levels more similar to double-positive cells rather than intermediate single-positive or single-positive levels
|
|
• in vitro, TCR/CD3 stimulation shows a 5-7 fold decrease in proliferating T cells compared to controls, specifically CD8+CD4lo and CD8+ CD4- populations
|
|
• null mice exhibit a consistent reduction in cellularity compared to wild-type or heterozygotes
|
|
• there is an increase in the population of the T cells in the late double negative (DN4) stage in the neonatal thymus
|
|
• percentage of double positive thymocytes is severely reduced
|
|
• CD8+ cells are greatly increased in number
• CD8+ populations in the thymus express TCR levels more similar to double-positive cells rather than intermediate single-positive or single-positive levels
|
|
• activated T cells are unable to go through normal cell divisions
|
|
• in vitro, TCR/CD3 stimulation shows a 5-7 fold decrease in proliferating T cells compared to controls, specifically CD8+CD4lo and CD8+ CD4- populations
|
|
• null mice exhibit a consistent reduction in cellularity compared to wild-type or heterozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not exhibit any signs of autoimmune disease
|
|
• during all stages of T cell development except DN1 that does not express the cre transgene
• 10-fold in double positive cells
|
|
• following treatment with CpG-ODNs, mice fail to exhibit an increased in CD4+ and CD8+ single positive T cells compared with wild-type mice
• however, untreated mice exhibit normal T cell proliferation and treated mice do exhibit an increase in macrophages in the spleen and liver as in wild-type mice
|
|
• when stimulated with IL2
|
|
• however, cortical area is normal
|
|
• almost 3-fold
|
|
• in the thymus more so than single conditional knock-outs
• in the blood, lymph nodes and spleen as in Nmt1tm1.1Poru conditional knock-outs
|
|
• at 6 months
|
|
• at 2 and 6 months more so than in either single conditional knock-out
|
|
• CD4+ and CD8+ single positive cells at 2 and 6 months
• following treatment with CpC-ODNs, mice fail to exhibit an increased in CD4+ and CD8+ single positive T cells compared with wild-type mice
|
|
• CD4+ T cells isolated from the lymph nodes and spleen exhibit a shift from naive to activated/memory phenotypes
|
|
• CD8+ T cells isolated from the lymph nodes and spleen exhibit a shift from naive to activated/memory phenotypes
|
|
• in mice sensitized with D-galactosamine hydrochloride and treated with staphylococcal enterotoxin B
|
|
• in mice sensitized with D-galactosamine hydrochloride and treated with staphylococcal enterotoxin B
|
|
• in mice sensitized with D-galactosamine hydrochloride and treated with staphylococcal enterotoxin B
|
|
• after TCR-independent activation
|
|
• after TCR-independent activation
|
|
• mice sensitized with D-galactosamine hydrochloride and treated with staphylococcal enterotoxin B exhibit reduced plasma levels of TNF, IL2 and IFN-gamma compared with wild-type mice
|
|
• in mice sensitized with D-galactosamine hydrochloride and treated with staphylococcal enterotoxin B
|
|
• in mice sensitized with D-galactosamine hydrochloride and treated with staphylococcal enterotoxin B
|
|
• in mice sensitized with D-galactosamine hydrochloride and treated with staphylococcal enterotoxin B
|
|
• during all stages of T cell development except DN1 that does not express the cre transgene
• 10-fold in double positive cells
|
|
• following treatment with CpG-ODNs, mice fail to exhibit an increased in CD4+ and CD8+ single positive T cells compared with wild-type mice
• however, untreated mice exhibit normal T cell proliferation and treated mice do exhibit an increase in macrophages in the spleen and liver as in wild-type mice
|
|
• when stimulated with IL2
|
|
• however, cortical area is normal
|
|
• at 6 months
|
|
• during all stages of T cell development except DN1 that does not express the cre transgene
• 10-fold in double positive cells
|
|
• following treatment with CpG-ODNs, mice fail to exhibit an increased in CD4+ and CD8+ single positive T cells compared with wild-type mice
• however, untreated mice exhibit normal T cell proliferation and treated mice do exhibit an increase in macrophages in the spleen and liver as in wild-type mice
|
|
• when stimulated with IL2
|
|
• however, cortical area is normal
|
|
• almost 3-fold
|
|
• in the thymus more so than single conditional knock-outs
• in the blood, lymph nodes and spleen as in Nmt1tm1.1Poru conditional knock-outs
|
|
• at 6 months
|
|
• at 2 and 6 months more so than in either single conditional knock-out
|
|
• CD4+ and CD8+ single positive cells at 2 and 6 months
• following treatment with CpC-ODNs, mice fail to exhibit an increased in CD4+ and CD8+ single positive T cells compared with wild-type mice
|
|
• CD4+ T cells isolated from the lymph nodes and spleen exhibit a shift from naive to activated/memory phenotypes
|
|
• CD8+ T cells isolated from the lymph nodes and spleen exhibit a shift from naive to activated/memory phenotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• moderate in the thymus
• in the blood, lymph nodes and spleen
|
|
• at 2 and 6 months, but less so than in conditional Nmt1tm1.1Poru and Nmt2tm1.1Poru knock-out mice
|
|
• CD4+ and CD8+ single positive cells
|
|
• CD4+ T cells isolated from the lymph nodes and spleen exhibit a shift from naive to activated/memory phenotypes
|
|
• CD8+ T cells isolated from the lymph nodes and spleen exhibit a shift from naive to activated/memory phenotypes
|
|
• moderate in the thymus
• in the blood, lymph nodes and spleen
|
|
• at 2 and 6 months, but less so than in conditional Nmt1tm1.1Poru and Nmt2tm1.1Poru knock-out mice
|
|
• CD4+ and CD8+ single positive cells
|
|
• CD4+ T cells isolated from the lymph nodes and spleen exhibit a shift from naive to activated/memory phenotypes
|
|
• CD8+ T cells isolated from the lymph nodes and spleen exhibit a shift from naive to activated/memory phenotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced in mutant mice
|
|
• reduced in mutant mice
|
|
• reduced in mutant mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• percentage of DP cells is reduced by 3-fold
|
|
• differentiation of thymocytes stalls at the DN4 stage, but some do make the transition to DP eventually
• absolute number of double negative (DN) thymocytes is unaltered, or elevated despite decrease in thymus cellularity
|
|
• CD8 + T cells are increased to compensate for reduced DP cell numbers
|
|
• 2- to 5-fold reduction in T cells in spleen is observed; decreased numbers of CD8+ and CD4+ populations is noted
|
|
• DP and CD4+ T cells express lower levels of CD4, and CD8+ cells range from CD4lo to CD4-
|
|
• 2- to 5-fold reduction in T cells in lymph nodes is observed; decreased numbers of CD8+ and CD4+ populations is noted
|
|
• percentage of DP cells is reduced by 3-fold
|
|
• differentiation of thymocytes stalls at the DN4 stage, but some do make the transition to DP eventually
• absolute number of double negative (DN) thymocytes is unaltered, or elevated despite decrease in thymus cellularity
|
|
• CD8 + T cells are increased to compensate for reduced DP cell numbers
|
|
• 2- to 5-fold reduction in T cells in spleen is observed; decreased numbers of CD8+ and CD4+ populations is noted
|
|
• DP and CD4+ T cells express lower levels of CD4, and CD8+ cells range from CD4lo to CD4-
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thymus cellularity is reduced by about 2.5 fold
|
|
• the percentage of double positive T cells in the thymus is reduced to 78.2% compared to 84.6% in wild-type mice
|
|
• thymus cellularity is reduced by about 2.5 fold
|
|
• the percentage of double positive T cells in the thymus is reduced to 78.2% compared to 84.6% in wild-type mice
|
|
• thymus cellularity is reduced by about 2.5 fold
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no abnormalities in T cell development are observed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 9% of the post-DN3 population is composed of CD4-DN4 cells compared to 25% in Smarca4tm1Tich/Smarca4tm1Tich Tg(Lck-cre)1Cwi Tg(LCKprBCL2L1)12Sjk mice
• 52% of the post-DN3 population is composed of CD4+DN4 cells compared to 39% in Smarca4tm1Tich/Smarca4tm1Tich Tg(Lck-cre)1Cwi Tg(LCKprBCL2L1)12Sjk mice
|
|
• 8-fold compared to in Smarca4tm1Gcr/Smarca4tm1Tich Tg(Lck-cre)1Cwi mice
|
|
• the DN2 population increases
• the DN3 population is rescued but is growth arrested
• the post-DN3 population is increased
|
|
• relative to DN4 cellularity
|
|
• 9% of the post-DN3 population is composed of CD4-DN4 cells compared to 25% in Smarca4tm1Tich/Smarca4tm1Tich Tg(Lck-cre)1Cwi Tg(LCKprBCL2L1)12Sjk mice
• 52% of the post-DN3 population is composed of CD4+DN4 cells compared to 39% in Smarca4tm1Tich/Smarca4tm1Tich Tg(Lck-cre)1Cwi Tg(LCKprBCL2L1)12Sjk mice
|
|
• 8-fold compared to in Smarca4tm1Gcr/Smarca4tm1Tich Tg(Lck-cre)1Cwi mice
|
|
• the DN2 population increases
• the DN3 population is rescued but is growth arrested
• the post-DN3 population is increased
|
|
• relative to DN4 cellularity
|
|
• 8-fold compared to in Smarca4tm1Gcr/Smarca4tm1Tich Tg(Lck-cre)1Cwi mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 14% of the post-DN3 population is composed of CD4+CD8- cells compared to 38% in Smarca4tm1Tich/Smarca4tm1Tich Tg(Lck-cre)1Cwi mice
• unlike in Smarca4tm1Tich/Smarca4tm1Tich Tg(Lck-cre)1Cwi mice, a CD4-CD8+ population analogous to immature single positive cells is observed
|
|
• post-DN3 cells are virtually absent
|
|
• 14% of the post-DN3 population is composed of CD4+CD8- cells compared to 38% in Smarca4tm1Tich/Smarca4tm1Tich Tg(Lck-cre)1Cwi mice
• unlike in Smarca4tm1Tich/Smarca4tm1Tich Tg(Lck-cre)1Cwi mice, a CD4-CD8+ population analogous to immature single positive cells is observed
|
|
• post-DN3 cells are virtually absent
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/16/2024 MGI 6.23 |
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