immune system
• in the thymus
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hematopoietic system
• in the thymus
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Allele Symbol Allele Name Allele ID |
Tg(TcrAND)53Hed transgene insertion 53, Stephen M Hedrick MGI:3053044 |
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Summary |
31 genotypes
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• in the thymus
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• in the thymus
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• TCR mediated positive T cell selection is unaffected by Tcfe2a deletion in T cells, in contrast to mice with total Tcfe2a deficiency
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N |
• in contrast to totally Tcfe2a-deficient mice, T cell specific Tcfe2a-deficient mice do not develop thymic lymphomas between 4 and 16 months of age
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• the immune response to strong T helper2 inducing conditions is absent
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• after 5 days of culture of antigen presenting cells with Schistosoma mansoni soluble egg antigen and pigeon cytochrome C, no IL-4 is produced as it is in wild-type cells
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• after 5 days of culture of antigen presenting cells with Schistosoma mansoni soluble egg antigen and pigeon cytochrome C, no IL-4 is produced as it is in wild-type cells
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• positive selection is diminished significantly
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• CD4 to CD8 ratio (% of mature CD4 and CD8 T cells) is 24 compared to 257 in non transgenic littermates
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• positive selection is diminished significantly
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• CD4 to CD8 ratio (% of mature CD4 and CD8 T cells) is 24 compared to 257 in non transgenic littermates
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• positive selection is diminished significantly
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• CD4 to CD8 ratio (% of mature CD4 and CD8 T cells) is 20 compared to 257 in non transgenic littermates
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• positive selection is diminished significantly
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• CD4 to CD8 ratio (% of mature CD4 and CD8 T cells) is 20 compared to 257 in non transgenic littermates
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• thymi have considerably greater cellularity (33-113% more cells) than littermates
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• mutant thymus has a 58% reduction in CD4+ thymocytes compared to littermates that only expressing the transgene
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• thymi have considerably greater cellularity (33-113% more cells) than littermates
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• mutant thymus has a 58% reduction in CD4+ thymocytes compared to littermates that only expressing the transgene
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• thymi have considerably greater cellularity (33-113% more cells) than littermates
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• higher double positive thymocyte numbers and fewer single-positive thymoyctes indicate a defect in positive selection
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• double-positive thymocytes are increased in mice
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• CD4 single-positive thymocyte numbers are reduced in these mice
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• higher double positive thymocyte numbers and fewer single-positive thymoyctes indicate a defect in positive selection
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• double-positive thymocytes are increased in mice
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• CD4 single-positive thymocyte numbers are reduced in these mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice die at 8 to 12 weeks of age
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• onset of lymphoproliferation is delayed compared to in Ctla4tm1All homozygotes
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• mice exhibit the expected skewing toward CD4+ T cells as in Tg(TcrAND)53Hed compared with wild-type mice
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• greater than 10-fold
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• in absolute numbers compared with Tg(TcrAND)53Hed mice
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• at 4 weeks, nearly all CD4+ T cells exhibit an activated phenotype unlike in Tg(TcrAND)53Hed mice
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• onset of lymphoproliferation is delayed compared to in Ctla4tm1All homozygotes
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• mice exhibit the expected skewing toward CD4+ T cells as in Tg(TcrAND)53Hed compared with wild-type mice
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• greater than 10-fold
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• in absolute numbers compared with Tg(TcrAND)53Hed mice
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• at 4 weeks, nearly all CD4+ T cells exhibit an activated phenotype unlike in Tg(TcrAND)53Hed mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• reduced percentage of CD4+ cells compared to mice wild-type for Vav1
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• reduced percentage of CD4+ cells compared to mice wild-type for Vav1
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• CD4+ T cells that do develop display sginficant reduction in expression of TCR alpha chain (40-50% compared to 90% in heterozygous mice littermates)
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• number of CD4-CD8- T cells is increased 5-7-fold compared to Itk-null mice
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• dramatic reduction in number and proportion of CD4+CD8- thymocytes is observed in thymus relative to control Itk-null mices
• profound reduction in CD4+ T cells in periphery is seen
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• CD4+ T cells that do develop display sginficant reduction in expression of TCR alpha chain (40-50% compared to 90% in heterozygous mice littermates)
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• number of CD4-CD8- T cells is increased 5-7-fold compared to Itk-null mice
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• dramatic reduction in number and proportion of CD4+CD8- thymocytes is observed in thymus relative to control Itk-null mices
• profound reduction in CD4+ T cells in periphery is seen
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 80% less B cells pulsed with antigen are conjugated by double positive thymocytes
• upon conjugation, thymocytes have impaired TCR-induced actin polymerization
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• there is an approximate 75% loss of transgenic TCR expression by CD4 single positive cells in the thymus
• the percentage of CD4 single positive T cells in the thymus is reduced almost 20-fold compared mice carrying the transgenic TCR alone
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• 80% less B cells pulsed with antigen are conjugated by double positive thymocytes
• upon conjugation, thymocytes have impaired TCR-induced actin polymerization
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• there is an approximate 75% loss of transgenic TCR expression by CD4 single positive cells in the thymus
• the percentage of CD4 single positive T cells in the thymus is reduced almost 20-fold compared mice carrying the transgenic TCR alone
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• 80% less B cells pulsed with antigen are conjugated by double positive thymocytes
• upon conjugation, thymocytes have impaired TCR-induced actin polymerization
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• 80% less B cells pulsed with antigen are conjugated by double positive thymocytes
• upon conjugation, thymocytes have impaired TCR-induced actin polymerization
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• the percentage of CD4 single positive T cells in the thymus is reduced almost 10-fold compared mice carrying the transgenic TCR alone
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• 80% less B cells pulsed with antigen are conjugated by double positive thymocytes
• upon conjugation, thymocytes have impaired TCR-induced actin polymerization
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• the percentage of CD4 single positive T cells in the thymus is reduced almost 10-fold compared mice carrying the transgenic TCR alone
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• 80% less B cells pulsed with antigen are conjugated by double positive thymocytes
• upon conjugation, thymocytes have impaired TCR-induced actin polymerization
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• positive selection is almost completely blocked in these mice
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• the proportion and number of double-positive thymocytes is greater than controls
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• very few single-positive thymocytes are generated in the thymus
• peripheral CD4 T cell numbers are severely reduced
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• very few single-positive thymocytes are generated in the thymus
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• positive selection is almost completely blocked in these mice
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• the proportion and number of double-positive thymocytes is greater than controls
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• very few single-positive thymocytes are generated in the thymus
• peripheral CD4 T cell numbers are severely reduced
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• very few single-positive thymocytes are generated in the thymus
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• nearly all CD4+ T cells in aged mice exhibit an activated phenotype unlike in Tg(TcrAND)53Hed mice
• however, lymph node T cells maintain a naive phenotype in young mice
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• CD4+ T cells exhibit increased primary and secondary antigen-specific proliferative responses compared to in Rag1tm1Mom/Rag1tm1Mom Tg(TcrAND)53Hed mice
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• in response to primary and secondary pigeon cytochrome c stimulation, the frequency of IL4-secreting T cells is increased compared to in Rag1tm1Mom/Rag1tm1Mom Tg(TcrAND)53Hed mice
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• nearly all CD4+ T cells in aged mice exhibit an activated phenotype unlike in Tg(TcrAND)53Hed mice
• however, lymph node T cells maintain a naive phenotype in young mice
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• CD4+ T cells exhibit increased primary and secondary antigen-specific proliferative responses compared to in Rag1tm1Mom/Rag1tm1Mom Tg(TcrAND)53Hed mice
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• CD4+ T cells exhibit increased primary and secondary antigen-specific proliferative responses compared to in Rag1tm1Mom/Rag1tm1Mom Tg(TcrAND)53Hed mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• following TCR stimulation, calcium mobilization in CD4+ T cells is decreased compared to in similarly treated wild-type cells
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• T cell proliferation is 2- to 3-fold lower following stimulation with I-EK+ or fibroblast APC expressing with I-EK+ and B7 molecules compared to in similarly treated wild-type cells
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• following stimulation with TCR-specific antigen
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• following stimulation with TCR-specific antigen
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• following TCR stimulation, calcium mobilization in CD4+ T cells is decreased compared to in similarly treated wild-type cells
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• T cell proliferation is 2- to 3-fold lower following stimulation with I-EK+ or fibroblast APC expressing with I-EK+ and B7 molecules compared to in similarly treated wild-type cells
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• T cell proliferation is 2- to 3-fold lower following stimulation with I-EK+ or fibroblast APC expressing with I-EK+ and B7 molecules compared to in similarly treated wild-type cells
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice show improved skin inflammation and scratching behavior and do not develop atopic dermatitis-like skin disease that is seen in Dock8tm1Ysfk/Dock8tm1Ysfk Tg(TcrAND)53Hed/0 mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• the activation threshold for transgenic CD4+ T cells is much lower than wild-type transgenic T cells
• both weak and strong peptide agonists caused increased amounts of proliferation compared to controls
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• the activation threshold for transgenic CD4+ T cells is much lower than wild-type transgenic T cells
• both weak and strong peptide agonists caused increased amounts of proliferation compared to controls
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• the activation threshold for transgenic CD4+ T cells is much lower than wild-type transgenic T cells
• both weak and strong peptide agonists caused increased amounts of proliferation compared to controls
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• thymocytes take longer to undergo positive selection than wild-type thymocytes based on expression of CD69 and HSA
• expression of CD5, which is correlated with TCR signal strength, is also decreased
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• the development of transgenic CD4 T cells is reduced 2- to 3-fold in these mice
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• thymocytes take longer to undergo positive selection than wild-type thymocytes based on expression of CD69 and HSA
• expression of CD5, which is correlated with TCR signal strength, is also decreased
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• the development of transgenic CD4 T cells is reduced 2- to 3-fold in these mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• thymocytes take longer to undergo positive selection than wild-type thymocytes based on expression of CD69 and HSA
• expression of CD5, which is correlated with TCR signal strength, is also decreased
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• there are almost no mature transgenic CD4 T cells in the periphery
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• thymocytes take longer to undergo positive selection than wild-type thymocytes based on expression of CD69 and HSA
• expression of CD5, which is correlated with TCR signal strength, is also decreased
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• there are almost no mature transgenic CD4 T cells in the periphery
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• reduction in TCRhi, CD69hi and CD69lo indicate inefficient positive selection
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• mice show altered proportion of double positive and CD4 populations
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• reduction in TCRhi, CD69hi and CD69lo indicate inefficient positive selection
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• mice show altered proportion of double positive and CD4 populations
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice show improved skin inflammation and scratching behavior compared to Dock8tm1Ysfk/Dock8tm1Ysfk Tg(TcrAND)53Hed/0 mice, without affecting serum IL-31 levels
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• T cells expressing the transgenic MHC class II-restricted TCR show diversion from the CD4+ lineage to the CD8+ lineage
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• T cells expressing the transgenic MHC class II-restricted TCR show diversion from the CD4+ lineage to the CD8+ lineage
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• the number of CD4 single-positive thymocytes are severely reduced in these mice
• peripheral CD4+ T cells are reduced by 75%
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• the number of CD4 single-positive thymocytes are severely reduced in these mice
• peripheral CD4+ T cells are reduced by 75%
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• negative selection of transgenic T cells leads to diminished CD4 T cells in the periphery
• apoptotic cells resulting from negative selection are found at the cortico-medullary and medullary portions of the thymus
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• T cells that escape central tolerance are able to respond to pigeon cytochrome C but 10 times as much protein is needed to get a comparable response to Tg(TcrAND)53Hed transgenic
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• block in T cell development is not rescued by transgene expression
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• increased ratio of CD4 SP to DP cells is detected in thymus
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• no increase in the double positive T cell population or thymic cellularity relative to Tcf12tm2Zhu homozygotes
• an increase in CD4 single positive cells is seen, indicating transgene expression can drive differentiation from the double positive (DP) to single positive (SP) stage
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• number of CD4 SP T cells is increased relative to nontransgenic Tcf12-null mice
• numbers of CD4 SP cells in thymus and peripheral lymphoid organs remains small relative to controls
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• block in T cell development is not rescued by transgene expression
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• increased ratio of CD4 SP to DP cells is detected in thymus
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• no increase in the double positive T cell population or thymic cellularity relative to Tcf12tm2Zhu homozygotes
• an increase in CD4 single positive cells is seen, indicating transgene expression can drive differentiation from the double positive (DP) to single positive (SP) stage
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• number of CD4 SP T cells is increased relative to nontransgenic Tcf12-null mice
• numbers of CD4 SP cells in thymus and peripheral lymphoid organs remains small relative to controls
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• decrease in the formation of CD4 single positive thymocytes
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• decrease in the formation of CD4 single positive thymocytes
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• normal MHC class-specific T cell development
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice develop an atopic dermatitis-like skin disease, with increased skin inflammation and scratching behavior
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• mice develop an atopic dermatitis-like skin disease, with increased skin inflammation and scratching behavior
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
atopic dermatitis | DOID:3310 |
OMIM:603165 OMIM:PS603165 |
J:305132 |
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice show improved skin inflammation and scratching behavior compared to Dock8tm1Ysfk/Dock8tm1Ysfk Tg(TcrAND)53Hed/0 mice, without affecting serum IL-31 levels
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice show improved skin inflammation and scratching behavior and do not develop atopic dermatitis-like skin disease that is seen in Dock8tm1Ysfk/Dock8tm1Ysfk Tg(TcrAND)53Hed/0 mice
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• T cells proliferate strongly when presented the carboxy-terminal fragment of pigeon cytochrome C antigen by autologous spleen cells
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• thymocytes proliferate strongly when presented the carboxy-terminal fragment of pigeon cytochrome C antigen by autologous spleen cells
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• 75% of thymocytes express high levels of CD3 compared to 18% of wild-type thymocytes
• 99% of thymocytes have detectable levels of CD3 compared to only 75% in wild-type thymocytes
• virtually all CD4 T cells in the periphery express the transgenic TCR
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• the transgenic TCR is positively selected for on this genetic background (H2-Ek) leading to a more efficient positive T cell selection that is skewed towards CD4 T cell production
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• the percentage of double-positive T cells in the thymus is 24% compared to 83% in wild-type mice
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• the CD4/CD8 single positive T cell ratio in the thymus is heavily skewed towards the CD4 population
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• the percentage of CD4 single positive T cells in the thymus is 63% compared to 13% in wild-type mice
• the percentage of CD 4 T cells in lymph nodes is 74% compared to 44% in wild-type controls
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• there is a two-fold reduction in CD8 single positive T cells in the thymus
• CD8 T cells are severely reduced in peripheral lymph nodes
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• T cells proliferate strongly when presented the carboxy-terminal fragment of pigeon cytochrome C antigen by autologous spleen cells
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• thymocytes proliferate strongly when presented the carboxy-terminal fragment of pigeon cytochrome C antigen by autologous spleen cells
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• 75% of thymocytes express high levels of CD3 compared to 18% of wild-type thymocytes
• 99% of thymocytes have detectable levels of CD3 compared to only 75% in wild-type thymocytes
• virtually all CD4 T cells in the periphery express the transgenic TCR
|
• the transgenic TCR is positively selected for on this genetic background (H2-Ek) leading to a more efficient positive T cell selection that is skewed towards CD4 T cell production
|
• the percentage of double-positive T cells in the thymus is 24% compared to 83% in wild-type mice
|
• the CD4/CD8 single positive T cell ratio in the thymus is heavily skewed towards the CD4 population
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• the percentage of CD4 single positive T cells in the thymus is 63% compared to 13% in wild-type mice
• the percentage of CD 4 T cells in lymph nodes is 74% compared to 44% in wild-type controls
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• there is a two-fold reduction in CD8 single positive T cells in the thymus
• CD8 T cells are severely reduced in peripheral lymph nodes
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• thymocytes proliferate strongly when presented the carboxy-terminal fragment of pigeon cytochrome C antigen by autologous spleen cells
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• T cells proliferate strongly when presented the carboxy-terminal fragment of pigeon cytochrome C antigen by autologous spleen cells
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• the percentage of CD4 single-positive thymocytes is greatly increased
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• the percentage of CD4 single-positive thymocytes is greatly increased
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• in mice with the H2k allele, the CD4:CD8 ratio is 15:1 to 100:1 compared to 3:1 in controls
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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 11/12/2024 MGI 6.24 |
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