immune system
N |
• mice have normal thymi and spleens, and normal distribution of single or double-positive and double-negative T cell populations relative to wild-type mice; numbers and ratios of B and T cells in spleen and lymph nodes are normal
(J:53513)
• CD4+ T cells have normal helper T cell function in presence of superantigen and exogenous Il-2 to overcome proliferative defect
(J:53513)
• lung tissue of allergen-treated mice show minimal inflammation compared to wild-type mice which display peribronchial or perivascular eosinophilia
(J:58987)
• most pancreatic islet cells appear normal in mutants not developing diabetes after streptozotocin treatment, while control pancreatic islets display insulitis; mutants developing diabetes after treatment display insulis in many islets
(J:118907)
|
• T cells exhibit defective proliferative responses to anti-CD3 and PMA/ionomycin stimulation compared to wild-type cells
(J:53513)
• splenocytes show reduced proliferation in culture, compared to wild-type cells, following stimulation with MOG peptide
(J:79107)
|
• Th1 T cell differentiation is blocked in mutants
|
• mutants treated with allergen show very mild eosinophilia compared to treated wild-type mice
|
• in spleens, there is a 9-fold decrease in frequency of spontaneously occurring memory B cells
• immunization with keyhole limpet hemocyanin for 10 days resulted in reduced generation of germinal center B cells compared to wild-type
|
• purified T cells only secrete Th2 cytokine secretion when stimulated with anti-CD3 and anti-CD28 antibodies; secretion of Il-2 is normal with anti-CD28 stimulation
(J:79107)
• splenocytes treated with anti-CD3 with or without anti-CD28 antibodies produce reduced levels of interferon gamma and Il-2 (Th1 cytokines) but increased levels of Il-4 and Il-10 (Th2 cytokines) while wild-type splenocytes produce both Th1 and Th2 cytokines
(J:118907)
|
• allo-specific CD8+ T cells lyse allotypic-target cells less effectively than wild-type CD8+ cells in culture; target cell specificity is comparable to wild-type cells
|
• stimulation of B cells in culture with anti-IgM, LPS, or anti-CD4 show reduced proliferative responses (5, 10, or 40% of wild-type, respectively)
|
• allergen-treated mice have attenuated IgE response compared to treated wild-type mice; serum levels are much lower than in wild-type mice after allergen treatment
|
• peritoneal macrophages produce less Il-6, Il-12p40, TNF alpha, and nitric oxide compared to wild-type cells upon stimulation with interferon gamma and/or LPS
|
• bone marrow-derived dendritic cells stimulated with LPS produce significantly less Il-12p40 and TNF alpha than stimulated wild-type dendritic cells
|
• T cells cultured +/- anti-CD3 in the presence of irradiated antigen-presenting cells produce <25% normal amounts of Il-2, Il-3, and GM-CSF relative to wild-type cells
(J:53513)
• splenocytes produce no detectable interferon gamma and reduced Il-2 concentrations in culture on stimulation with MOG peptide relative to wild-type splenocytes, whereas Il-4 production is substantially increased
(J:79107)
• cultured antigen-presenting cells (APCs) from spleens and microglia or astrocytes produce significantly less Il-12 p40 upon LPS or MOG peptide stimulation
(J:79107)
|
• >70% of control mice treated with low dose streptozotocin for 5 days develop diabetes starting ~8 and 12 days after the first injection, but only 29% of mutants develop diabetes
|
• EAE developed in only 16% of mice immunized with MOG38-50, compared to EAE observed in 100% of control mice; onset in mutants is delayed by ~12 days relative to controls (mean: 28+/-1 days vs 16+/-1 in controls)
• no lesions or demyelination is observed in CNS of mutants without symptoms of EAE compared to multiple inflammatory foci in cerebrum, cerebellum, brain stem, and spinal cord, with severe demyelination observed in controls with EAE
|
hematopoietic system
• stimulation of B cells in culture with anti-IgM, LPS, or anti-CD4 show reduced proliferative responses (5, 10, or 40% of wild-type, respectively)
|
• T cells exhibit defective proliferative responses to anti-CD3 and PMA/ionomycin stimulation compared to wild-type cells
(J:53513)
• splenocytes show reduced proliferation in culture, compared to wild-type cells, following stimulation with MOG peptide
(J:79107)
|
• Th1 T cell differentiation is blocked in mutants
|
• mutants treated with allergen show very mild eosinophilia compared to treated wild-type mice
|
• in spleens, there is a 9-fold decrease in frequency of spontaneously occurring memory B cells
• immunization with keyhole limpet hemocyanin for 10 days resulted in reduced generation of germinal center B cells compared to wild-type
|
• allergen-treated mice have attenuated IgE response compared to treated wild-type mice; serum levels are much lower than in wild-type mice after allergen treatment
|
• purified T cells only secrete Th2 cytokine secretion when stimulated with anti-CD3 and anti-CD28 antibodies; secretion of Il-2 is normal with anti-CD28 stimulation
(J:79107)
• splenocytes treated with anti-CD3 with or without anti-CD28 antibodies produce reduced levels of interferon gamma and Il-2 (Th1 cytokines) but increased levels of Il-4 and Il-10 (Th2 cytokines) while wild-type splenocytes produce both Th1 and Th2 cytokines
(J:118907)
|
• allo-specific CD8+ T cells lyse allotypic-target cells less effectively than wild-type CD8+ cells in culture; target cell specificity is comparable to wild-type cells
|
• peritoneal macrophages produce less Il-6, Il-12p40, TNF alpha, and nitric oxide compared to wild-type cells upon stimulation with interferon gamma and/or LPS
|
cellular
• CD40 treatment of B cells induces fewer mutant cells to progress to S and G2/M phases than wild-type cells, while number of mutant cells entering cell cycle after IgM or LPS treatment is dramatically decreased compared to treated wild-type cells
|
• cultured cortical neurons exposed to amyloid beta show similar levels of neurotoxicity (~50%) to wild-type neurons; when exposed to amyloid beta with mGlu5 receptor agonists, neurons show decreased survival (~40%) whereas wild-type neurons are completely protected from neurotoxicity induced by amyloid beta alone
|
• growth factor withdrawal from cultured bone marrow dendritic cells accelerates death of granulocytes and macrophages, but not dendritic cells from mutant animals
|
• stimulation of B cells in culture with anti-IgM, LPS, or anti-CD4 show reduced proliferative responses (5, 10, or 40% of wild-type, respectively)
|
• T cells exhibit defective proliferative responses to anti-CD3 and PMA/ionomycin stimulation compared to wild-type cells
(J:53513)
• splenocytes show reduced proliferation in culture, compared to wild-type cells, following stimulation with MOG peptide
(J:79107)
|
• when cultured B cells are stimulated with anti-IgM, LPS, or anti-CD40, mutant cells fail to initiate DNA synthesis until 26-32 hours after culture initiation; magnitude of response is ~10% of wild-type level
|
nervous system
• cultured cortical neurons exposed to amyloid beta show similar levels of neurotoxicity (~50%) to wild-type neurons; when exposed to amyloid beta with mGlu5 receptor agonists, neurons show decreased survival (~40%) whereas wild-type neurons are completely protected from neurotoxicity induced by amyloid beta alone
|
homeostasis/metabolism
• when cultured B cells are stimulated with anti-IgM, LPS, or anti-CD40, mutant cells fail to initiate DNA synthesis until 26-32 hours after culture initiation; magnitude of response is ~10% of wild-type level
|
respiratory system
N |
• lung tissue of allergen-treated mice show minimal inflammation compared to wild-type mice which display peribronchial or perivascular eosinophilia
• with allergen treatment after OVA sensitization, mice do not show airway hyperresponsiveness (AHR) like wild-type mice; pulmonary resistance in response to methacholine is not different from PBS control mutants and wild-type mice treated with methacholine show much higher airway resistances at each dose
|