Analysis Tools
mortality/aging
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• reduced life span
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growth/size/body
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• reduced body size at birth, 4 and 20 weeks of age
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• reduced body weight at 4 and 20 weeks of age
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• growth retardation at 4 months of age
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cellular
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• severely impaired recombination signal (RS) joining in mutant embryonic stem cells
• largely preserved coding joins formation, but imprecise RS joins in thymocytes
• extensive deletions within RS joins in thymocytes
• relatively normal joins could be recovered
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• increased radiation sensitivity in mutant mouse embryonic fibroblasts
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• markedly reduced viability and increased apoptosis when simultaneously stained for annexin-V and 7-Aminoactinomycin D (7-AAD) for in vitro activated mutant splenic T cells
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• dramatic defect of splenic T cell proliferation, as assessed by 5,6-carboxyfluorescein succinimidyl ester (CFSE) dilution in vitro in the presence of anti-CD3 monoclonal antibody (mAb) in combination with either anti-CD28 mAb or IL-2
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• 20% of the metaphases in mutant T cells contain aberrancies with the majority being chromosomal breaks and translocations, as compared to <2% chromosomal aberrancies in heterozygous cells
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reproductive system
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• fertility of mutant mice is severely compromised
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immune system
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• significantly reduced B220+ cells in the bone marrow
• majority of B220+ IgM- cells expressed CD43, indicating an incomplete block at the pro-B cell stage
• significantly reduced B220+ IgM+ B cells in the spleen
• a restricted repertoire of the splenic B cells
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• clonal rearrangements or deletion of the Jbeta1 cluster in the vast majority of the tumors (8 of 13)
• clonal rearrangements involving the Jbeta2 cluster in several of the tumors
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• a restricted T cell receptor (TCR) Vbeta repertoire in the spleen
• a largely polyclonal TCR Vbeta repertoire in the thymus
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• drastically reduced absolute number of CD4_CD8_ double-negative (DN) T cell
• accumulation of DN thymocytes at the CD44_ CD25+ DN3 stage of development
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• drastically reduced absolute number of CD4+ CD8+ double-positive T cell
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• a lower number of transitional, follicular, and marginal zone splenic B cells
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• drastically reduced absolute number of CD4+ T cell in the mutant thymus and spleen
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• drastically reduced absolute number of CD8+ T cell in the mutant thymus and spleen
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• CD4+ CD25hi Foxp3+ regulatory T cells in mesenteric lymph nodes
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• mild architectural abnormalities with conserved demarcation between the cortex and the small-sized medulla
• overall preservation of the thymic architecture and of the corticomedullary demarcation
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small thymus
(
J:157574
)
|
• decreased number in total thymic cellularity
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• significant proportion (13/44) of them develop thymic tumors
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small spleen
(
J:157574
)
|
• markedly reduced total cellularity in the spleen
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• markedly reduced viability and increased apoptosis when simultaneously stained for annexin-V and 7-Aminoactinomycin D (7-AAD) for in vitro activated mutant splenic T cells
|
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• modest inflammatory infiltrates (mainly composed of T lymphocytes and neutrophils) in the gut
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• spontaneously produced higher titers of 2,4,6-trinitrophenol (TNP)-specific IgM and IgG
• following immunization with the T-independent type II antigen TNP-Ficoll or with T-dependent antigen TNP-keyhole limpet hemocyanin (KLH), produce lower amounts of antigen-specific IgM and IgG antibodies
• no high-affinity TNP-specific IgG antibodies detected after secondary immunization with TNP-KLH
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• significantly reduced IgA serum level at 8 weeks old
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• following immunization with the T-independent type II antigen TNP-Ficoll or with T-dependent antigen TNP-keyhole limpet hemocyanin (KLH), produce lower amounts of antigen-specific IgG antibodies
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• significantly reduced IgG2b serum level at 8 weeks old
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• significantly reduced IgG3 serum level at 8 weeks old
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• significantly reduced IgM serum level at 8 weeks old
• following immunization with the T-independent type II antigen TNP-Ficoll or with T-dependent antigen TNP-keyhole limpet hemocyanin (KLH), produce lower amounts of antigen-specific IgM antibodies
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• the vast majority of the CD4+ or CD8+ splenic T cells are CD44+ CD62L_, suggesting in vivo activation
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• dramatic defect of splenic T cell proliferation, as assessed by 5,6-carboxyfluorescein succinimidyl ester (CFSE) dilution in vitro in the presence of anti-CD3 monoclonal antibody (mAb) in combination with either anti-CD28 mAb or IL-2
|
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• reduced IFN-gamma secretion in splenic T cells
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• reduced IL-13 secretion in splenic T cells
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• modest inflammatory infiltrates (mainly composed of T lymphocytes and neutrophils) in the liver
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liver/biliary system
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• modest inflammatory infiltrates (mainly composed of T lymphocytes and neutrophils) in the liver
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digestive/alimentary system
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• colon adenocarcinoma in 4 out of 44 mice
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• modest inflammatory infiltrates (mainly composed of T lymphocytes and neutrophils) in the gut
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neoplasm
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• colon adenocarcinoma in 4 out of 44 mice
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• significant proportion (13/44) of them develop thymic tumors
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• medulloblastoma in 1 out of 44 mice
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hematopoietic system
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• markedly reduced viability and increased apoptosis when simultaneously stained for annexin-V and 7-Aminoactinomycin D (7-AAD) for in vitro activated mutant splenic T cells
|
|
• mild architectural abnormalities with conserved demarcation between the cortex and the small-sized medulla
• overall preservation of the thymic architecture and of the corticomedullary demarcation
|
small thymus
(
J:157574
)
|
• decreased number in total thymic cellularity
|
|
• significant proportion (13/44) of them develop thymic tumors
|
|
• significantly reduced B220+ cells in the bone marrow
• majority of B220+ IgM- cells expressed CD43, indicating an incomplete block at the pro-B cell stage
• significantly reduced B220+ IgM+ B cells in the spleen
• a restricted repertoire of the splenic B cells
|
|
• clonal rearrangements or deletion of the Jbeta1 cluster in the vast majority of the tumors (8 of 13)
• clonal rearrangements involving the Jbeta2 cluster in several of the tumors
|
|
• a restricted T cell receptor (TCR) Vbeta repertoire in the spleen
• a largely polyclonal TCR Vbeta repertoire in the thymus
|
|
• drastically reduced absolute number of CD4_CD8_ double-negative (DN) T cell
• accumulation of DN thymocytes at the CD44_ CD25+ DN3 stage of development
|
|
• drastically reduced absolute number of CD4+ CD8+ double-positive T cell
|
|
• a lower number of transitional, follicular, and marginal zone splenic B cells
|
|
• drastically reduced absolute number of CD4+ T cell in the mutant thymus and spleen
|
|
• drastically reduced absolute number of CD8+ T cell in the mutant thymus and spleen
|
|
• CD4+ CD25hi Foxp3+ regulatory T cells in mesenteric lymph nodes
|
small spleen
(
J:157574
)
|
• markedly reduced total cellularity in the spleen
|
|
• spontaneously produced higher titers of 2,4,6-trinitrophenol (TNP)-specific IgM and IgG
• following immunization with the T-independent type II antigen TNP-Ficoll or with T-dependent antigen TNP-keyhole limpet hemocyanin (KLH), produce lower amounts of antigen-specific IgM and IgG antibodies
• no high-affinity TNP-specific IgG antibodies detected after secondary immunization with TNP-KLH
|
|
• significantly reduced IgA serum level at 8 weeks old
|
|
• following immunization with the T-independent type II antigen TNP-Ficoll or with T-dependent antigen TNP-keyhole limpet hemocyanin (KLH), produce lower amounts of antigen-specific IgG antibodies
|
|
• significantly reduced IgG2b serum level at 8 weeks old
|
|
• significantly reduced IgG3 serum level at 8 weeks old
|
|
• significantly reduced IgM serum level at 8 weeks old
• following immunization with the T-independent type II antigen TNP-Ficoll or with T-dependent antigen TNP-keyhole limpet hemocyanin (KLH), produce lower amounts of antigen-specific IgM antibodies
|
|
• the vast majority of the CD4+ or CD8+ splenic T cells are CD44+ CD62L_, suggesting in vivo activation
|
|
• dramatic defect of splenic T cell proliferation, as assessed by 5,6-carboxyfluorescein succinimidyl ester (CFSE) dilution in vitro in the presence of anti-CD3 monoclonal antibody (mAb) in combination with either anti-CD28 mAb or IL-2
|
endocrine/exocrine glands
|
• mild architectural abnormalities with conserved demarcation between the cortex and the small-sized medulla
• overall preservation of the thymic architecture and of the corticomedullary demarcation
|
small thymus
(
J:157574
)
|
• decreased number in total thymic cellularity
|
|
• significant proportion (13/44) of them develop thymic tumors
|
nervous system
|
• medulloblastoma in 1 out of 44 mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| DNA ligase IV deficiency | DOID:0060021 |
OMIM:606593 |
J:157574 | |
