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Allele Symbol Allele Name Allele ID |
Tg(TcrLCMV)327Sdz transgene insertion 327, Birgit Ledermann MGI:2665105 |
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| Summary |
21 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• CD8 T cells require 10- to 100-fold more antigen (gp33 peptide) to induce the same amount of proliferation as cells from Tg(TcrLCMV)327Sdz mice
• however, addition of IL2 partially restores CD8 T cell proliferation in response to gp33 peptide
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• in mice treated gp33 peptide
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• after 3 days, cytotoxic T lymphocyte (CTL) activation in mice treated with gp33 peptide is decreased compared to in Tg(TcrLCMV)327Sdz mice
• splenocytes exposed to gp33 exhibit impaired CTL activation compared with similarly treated cells from Tg(TcrLCMV)327Sdz mice
• however, CTL activation in mice treated with gp33 peptide is normal at day 1 and treatment with IL2 restores CTL in splenocytes
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• cytotoxic T lymphocyte anergy is induced in mice treated with gp33 peptide unlike in similarly treated Tg(TcrLCMV)327Sdz mice
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• CD8 T cells require 10- to 100-fold more antigen (gp33 peptide) to induce the same amount of proliferation as cells from Tg(TcrLCMV)327Sdz mice
• however, addition of IL2 partially restores CD8 T cell proliferation in response to gp33 peptide
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• in mice treated gp33 peptide
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• after 3 days, cytotoxic T lymphocyte (CTL) activation in mice treated with gp33 peptide is decreased compared to in Tg(TcrLCMV)327Sdz mice
• splenocytes exposed to gp33 exhibit impaired CTL activation compared with similarly treated cells from Tg(TcrLCMV)327Sdz mice
• however, CTL activation in mice treated with gp33 peptide is normal at day 1 and treatment with IL2 restores CTL in splenocytes
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• CD8 T cells require 10- to 100-fold more antigen (gp33 peptide) to induce the same amount of proliferation as cells from Tg(TcrLCMV)327Sdz mice
• however, addition of IL2 partially restores CD8 T cell proliferation in response to gp33 peptide
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• in mice treated gp33 peptide
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• after injection with streptozocin for 5 consecutive days, blood glucose in caspase-3-homozygous transgenic mice remains normoglycemic for the duration of the study
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• adoptive transfer of labeled Tg(TcrLCMV)327Sdz-transgene positive T cells, examination of pancreatic draining lymph nodes showed that only 45% of the transferred T cells had undergone proliferation compared to 62% in caspase-3-heterozygous transgenic recipients
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• in CD8+ T cells isolated from pancreatic draining or non-draining lymph nodes of streptozocin-treated mice, 32% of the CD8+ cells are CD69hi positive and 9% respectively, compared to corresponding values of 3% and 5% respectively in caspase-3-heterozygous transgenic mice
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• in CD8+ T cells isolated from pancreatic draining or non-draining lymph nodes of streptozocin-treated mice, 32% of the CD8+ cells are CD69hi positive and 9% respectively, compared to corresponding values of 3% and 5% respectively in caspase-3-heterozygous transgenic mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• generation of CD8+/V alpha2high thymocytes and lymph node T cells is normal
• double negative and double positive cells from thymi of female mutants and wild-type mice have similar levels of CD5 expression
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• single positive thymocytes have lower CD5 surface expression than thymocytes from wild-type Tg(TcrLCMV)327Sdz or Tg(TcraH-Y,TcrbH-Y)71Vbo mice, or Zap70tm1.1Mmal/ Tg(TcrLCMV)327Sdz or Zap70tm1.1Mmal/ Tg(TcraH-Y,TcrbH-Y)71Vbo double mutants
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• single positive thymocytes have lower CD5 surface expression than thymocytes from wild-type Tg(TcrLCMV)327Sdz or Tg(TcraH-Y,TcrbH-Y)71Vbo mice, or Zap70tm1.1Mmal/ Tg(TcrLCMV)327Sdz or Zap70tm1.1Mmal/ Tg(TcraH-Y,TcrbH-Y)71Vbo double mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• generation of CD8+/V alpha2high thymocytes and lymph node T cells is normal
• double negative and double positive cells from thymi of female mutants and wild-type mice have similar levels of CD5 expression
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• when challenged with subnanomolar concentrations of p33 peptide in vitro, T cells proliferate more than wild-type Tg(TcrLCMV)327Sdz T cells
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• T cells produce 2-3-fold more IL-2 in response to graded p33 concentrations in vitro compared to stimulated wild-type Tg(TcrLCMV)327Sdz or Zap70tm2.1Mmal/ Tg(TcrLCMV)327Sdz T cells
• this is not observed at a single-cell level of cytokine production, indicating that increased IL-2 is result of greater T cell numbers
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• when challenged with subnanomolar concentrations of p33 peptide in vitro, T cells proliferate more than wild-type Tg(TcrLCMV)327Sdz T cells
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• when challenged with subnanomolar concentrations of p33 peptide in vitro, T cells proliferate more than wild-type Tg(TcrLCMV)327Sdz T cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• upon antigenic stimulation by injection of LCMV, caspase activation and DNA fragmentation in the TCRalphabetaint thymocyte population is reduced compared to Map2k6-sufficient transgenic mice, while levels in the TCRalphabetahi population are comparable
• upon antigenic stimulation by injection of LCMV, deletion of TCR CD4hiCD8hi cells is less efficient than in Map2k6-sufficient transgenic mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD8 T cells require 10- to 100-fold more antigen (gp33 peptide) to induce the same amount of proliferation as cells from Tg(TcrLCMV)327Sdz mice
• however, addition of IL2 restores CD8 T cell proliferation in response to gp33 peptide
|
|
• in mice treated gp33 peptide
|
|
• after 3 days, cytotoxic T lymphocyte (CTL) activation in mice treated with gp33 peptide is decreased compared to in Tg(TcrLCMV)327Sdz mice
• splenocytes exposed to gp33 exhibit impaired CTL activation compared with similarly treated cells from Tg(TcrLCMV)327Sdz mice
• however, CTL activation in mice treated with gp33 peptide is normal at day 1 and treatment with IL2 restores CTL in splenocytes
|
|
• cytotoxic T lymphocyte anergy in mice treated with gp33 peptide is induced unlike in similarly treated Tg(TcrLCMV)327Sdz mice
|
|
• CD8 T cells require 10- to 100-fold more antigen (gp33 peptide) to induce the same amount of proliferation as cells from Tg(TcrLCMV)327Sdz mice
• however, addition of IL2 restores CD8 T cell proliferation in response to gp33 peptide
|
|
• in mice treated gp33 peptide
|
|
• after 3 days, cytotoxic T lymphocyte (CTL) activation in mice treated with gp33 peptide is decreased compared to in Tg(TcrLCMV)327Sdz mice
• splenocytes exposed to gp33 exhibit impaired CTL activation compared with similarly treated cells from Tg(TcrLCMV)327Sdz mice
• however, CTL activation in mice treated with gp33 peptide is normal at day 1 and treatment with IL2 restores CTL in splenocytes
|
|
• CD8 T cells require 10- to 100-fold more antigen (gp33 peptide) to induce the same amount of proliferation as cells from Tg(TcrLCMV)327Sdz mice
• however, addition of IL2 restores CD8 T cell proliferation in response to gp33 peptide
|
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• in mice treated gp33 peptide
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• survival time at which half of the mutants are sacrificed or die due to illness is 101 days
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• 100% of mutants develop thymic lymphoma within the same accelerated time frame as mutants heterozygous for Rag1 and hemizygous for the two transgenes
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• 100% of mutants develop thymic lymphoma within the same accelerated time frame as mutants heterozygous for Rag1 and hemizygous for the two transgenes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• survival time at which half of the mutants are sacrificed or die due to illness is 110 days
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• 100% incidence of thymoma
• tumorigenesis is accelerated compared to mice hemizygous for Tg(LPV-TAg1135)11Tvd and heterozygous for Rag1
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• 100% incidence of thymoma
• tumorigenesis is accelerated compared to mice hemizygous for Tg(LPV-TAg1135)11Tvd and heterozygous for Rag1
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• CD8+ T cells show no differences in prevalence, numbers, or TCR expression levels relative to Arts1-sufficient Tg(TcrLCMV)327Sdz mice (on Rag2-null background)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• CD8 thymocyte positive selection is impaired: the proportion of CD8+ single positive thymocytes is reduced by about 75% and gating on TCRhi cells show almost 90% reduction
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• the proportion of CD8+ single positive thymocytes is reduced by about 75% and gating on TCRhi cells show almost 90% reduction
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• CD8 thymocyte positive selection is impaired: the proportion of CD8+ single positive thymocytes is reduced by about 75% and gating on TCRhi cells show almost 90% reduction
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• the proportion of CD8+ single positive thymocytes is reduced by about 75% and gating on TCRhi cells show almost 90% reduction
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• dramatic reduction of thymic cellularity
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• altered thymic selection process
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• enhanced positive selection of T cells and partial conversion of positive selection to negative selection
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• dramatic reduction of thymic cellularity
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• altered thymic selection process
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• enhanced positive selection of T cells and partial conversion of positive selection to negative selection
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• dramatic reduction of thymic cellularity
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• when naive CD8 T cells transferred into B6 Ptprc
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• skewing of thymocytes to the single CD8+ mature phenotype, indicating that thymocytes are positively selected
• however, double transgenic mice are able to respond by proliferation to LCMV antigens at the same magnitude as single Tg(TcrLCMV)327Sdz mice and cytotoxic T lymphocytes are able to respond to LCMV infection as in controls
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| N |
• mice do not develop diabetes and exhibit normal islet architecture with no evidence of insulitis
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• mice immunized with lymphocytic choriomeningitis virus (LCMV) develop hyperglycemia 3 to 4 days after infection
• a variant LCM virus, 8.7, does not induce diabetes in mice
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• mice immunized with LCMV develop glucosuria 3 to 4 days after infection
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• skewing of thymocytes to the single CD8+ mature phenotype, indicating that thymocytes are positively selected
• however, double transgenic mice are able to respond by proliferation to LCMV antigens at the same magnitude as single Tg(TcrLCMV)327Sdz mice and cytotoxic T lymphocytes are able to respond to LCMV infection as in controls
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• mice immunized with LCMV develop glucosuria 3 to 4 days after infection
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hyperglycemia is followed by ketosis, wasting, and death
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• complete beta-cell destruction
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• ongoing insulitis is seen at 10 weeks of age, with a diminished, but still present, mass of beta cells
• 4 week old mice show a mixture of a few cD8+ and CD4+ T lymphocytes and an increase in the number of macrophages surrounding pancreatic islets, while 9 week old mice show severe insulitis and periinsulitis with CD8+ and CD4+ T lymphocytes, macrophages and B lymphocytes infiltrating the islets
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• 9 week old mice show severe periinsulitis
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• mice spontaneously become diabetic with a median age of hyperglycemia onset of 9-10 weeks of age
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• ongoing insulitis is seen at 10 weeks of age, with a diminished, but still present, mass of beta cells
• 4 week old mice show a mixture of a few cD8+ and CD4+ T lymphocytes and an increase in the number of macrophages surrounding pancreatic islets, while 9 week old mice show severe insulitis and periinsulitis with CD8+ and CD4+ T lymphocytes, macrophages and B lymphocytes infiltrating the islets
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• 9 week old mice show severe periinsulitis
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| type 1 diabetes mellitus | DOID:9744 |
OMIM:222100 |
J:209714 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not develop spontaneous diabetes or diabetes when infected with a recombinant vaccinia virus expressing GP
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice have substantial numbers of transgenic CD4+ T cells while having a complete absence of transgenic CD8+ T cells, which is a reversal of the T cell populations that normally develop in mice carrying just the Tg(TcrLCMV)327Sdz allele
• the CD4 T cells bear high levels of the transgenic TCR, express CD154 upon activation, and have other hallmarks (lack perforin and IFN-gamma expression) of truly belonging to the CD4 lineage and not the CD8 lineage
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• mice have substantial numbers of transgenic CD4+ T cells while having a complete absence of transgenic CD8+ T cells, which is a reversal of the T cell populations that normally develop in mice carrying just the Tg(TcrLCMV)327Sdz allele
• the CD4 T cells bear high levels of the transgenic TCR, express CD154 upon activation, and have other hallmarks (lack perforin and IFN-gamma expression) of truly belonging to the CD4 lineage and not the CD8 lineage
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• the presence of the T cell receptor transgene does not increase susceptibility to type 1 diabetes, even in the presence of this transgene NOD mice homozygous for the scid mutation do not develop type 1 diabetes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the rate and frequency of type 1 diabetes development in transgenic NOD females is the same as that in NOD females lacking the transgene
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• response of uninfected transgenic Mlsa spleen cells to LCMV is reduced ~3-fold
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• numbers of double-positive thymocytes and CD8+ thymocytes are drastically reduced in transgenic mice
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• numbers of CD4+CD8+ thymocytes are drastically reduced in LCMV-tolerant (carrier) transgenic mice
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• number of CD8+ T cells in spleens of transgenic Mlsa mice is reduced 4-fold compared to uninfected transgenic Mlsb but ~4-fold higher than LCMV-infected Mlsb mice
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• lysis of LCMV-infected target cells is decreased ~3-fold in uninfected transgenic mice positive for mixed-lymphocyte stimulatory (Mlsa) antigen compared to transgenic mice positive for Mlsb antigen
• LCMV-infected Mlsb show decreased significantly reduced proliferation and specific lysis compared to uninfected transgenic mice
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• response of uninfected transgenic Mlsa spleen cells to LCMV is reduced ~3-fold
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• numbers of double-positive thymocytes and CD8+ thymocytes are drastically reduced in transgenic mice
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• numbers of CD4+CD8+ thymocytes are drastically reduced in LCMV-tolerant (carrier) transgenic mice
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• number of CD8+ T cells in spleens of transgenic Mlsa mice is reduced 4-fold compared to uninfected transgenic Mlsb but ~4-fold higher than LCMV-infected Mlsb mice
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• lysis of LCMV-infected target cells is decreased ~3-fold in uninfected transgenic mice positive for mixed-lymphocyte stimulatory (Mlsa) antigen compared to transgenic mice positive for Mlsb antigen
• LCMV-infected Mlsb show decreased significantly reduced proliferation and specific lysis compared to uninfected transgenic mice
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• numbers of double-positive thymocytes and CD8+ thymocytes are drastically reduced in transgenic mice
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• response of uninfected transgenic Mlsa spleen cells to LCMV is reduced ~3-fold
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• T cells expressing the transgene preferentially develop into CD8+ peripheral T cells
• there is only minimal rearrangement of endogenous TCRalpha chains needed in double-positive thymocytes to express a transgenic TCR, so that mice have very few CD4 single-positive thymocytes or CD4+ peripheral T cells
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• very few CD4+T cells are found in the thymus or periphery
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• T cells expressing the transgene preferentially develop into CD8+ peripheral T cells
• there is only minimal rearrangement of endogenous TCRalpha chains needed in double-positive thymocytes to express a transgenic TCR, so that mice have very few CD4 single-positive thymocytes or CD4+ peripheral T cells
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• very few CD4+T cells are found in the thymus or periphery
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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 04/16/2024 MGI 6.23 |
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