immune system
• is noted in some cases
|
• neutrophils fail to migrate efficiently across a filter in response to different concentrations of the chemoattractant MLP
• neutrophils have defects in actin polymerization near the leading edge of cellular membranes
|
• T cells have reduced proliferation in response to CD3 and CD28 stimulation and do not increase proliferation when activated in the presence of IL-2
|
• macrophage phagocytosis of bacteria is impaired by more than half
|
• neutrophils have a 3-fold decrease in their ability to phagocytose fluorescent-conjugated beads and bacteria in response to MLP stimulation
|
• mutant bone marrow cells poorly reconstitute the thymi of immunideficient hosts with low numbers of mature T cells resulting in the periphery
• in these same recipient mice, mature B cells fail to develop unless recipient animals are also lethally irradiated in which case low numbers of B cells are found in the periphery
|
• the generation in vitro of Th17 T cells from mutant nave CD4+ T cells is enhanced compared to controls
|
• the percentage of double negative thymocytes is increased more than five fold as alphabeta T cell development is delayed at the DN3 to DN4 transition
|
• the percentage of double positive thymocytes is decreased as alphabeta T cell development is impaired at the double negative stage
|
• the ratio of FoxP3+CD4+ T cells to FoxP3-CD4+ T cells is enhanced in these mice both in the thymus and in the spleen
|
• lymphocytes numbers are decreased about 3.5-fold in the blood
|
• B cell numbers in the periphery are reduced by at least 75%
|
• CD4+ T cell numbers are decreased in the thymus and in the periphery by at least 75%
|
• CD8+ T cell numbers are decreased in the thymus and in the periphery by at least 75%
|
• gamma-delta T cell numbers are reduced in the thymus by 6-fold and in the spleen by 3-fold
|
• white blood cell count in the blood is increased about 2- to 2.5- fold
|
• neutrophil numbers are increased 25-fold in the blood
|
• serum IL-17 levels are about 3-fold higher than controls
|
• serum IL-6 levels are more than 2-fold higher than controls
|
• thymi are under developed and lack a clear cortical/medullary architecture
|
• thymus numbers are reduced by 30-fold
|
• spleen hyperplasia occurs in these mice even though lymphoid cells are depleted, because of marked proliferation of myeloid and erythroid progenitors
|
• lymph node hypoplasia is commonly found in these mice
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• T cells produce 15-fold more IL-17 when activated
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• activated T cells secrete 2-fold more IL-6 than controls
|
• activated T cells secrete 2-fold more TNF than controls
|
• is noted in some cases
|
• is noted in some cases
|
growth/size/body
• some inflammation of the thoracic pleura is noted
|
• spleen hyperplasia occurs in these mice even though lymphoid cells are depleted, because of marked proliferation of myeloid and erythroid progenitors
|
homeostasis/metabolism
amyloidosis
(
J:141377
)
• occurs occasionally in these mice, especially in the liver
|
• serum IL-17 levels are about 3-fold higher than controls
|
• serum IL-6 levels are more than 2-fold higher than controls
|
cardiovascular system
• myocardial fibrosis occasionally occurs in these mice
|
• is noted in some cases
|
respiratory system
• is noted in some cases
|
liver/biliary system
• is noted in some cases
|
• dense amyloid accumulations containing foci of mineral at the margins of the liver is observed
|
renal/urinary system
• an increase in mesangial matrix and cellularity in the kidneys of these mice are consistent with membranoproliferative glomerulopathy
• these lesions are commonly found in this mouse strain
|
reproductive system
• inflammation of the epididymis is sometimes observed
|
hematopoietic system
• neutrophils fail to migrate efficiently across a filter in response to different concentrations of the chemoattractant MLP
• neutrophils have defects in actin polymerization near the leading edge of cellular membranes
|
• T cells have reduced proliferation in response to CD3 and CD28 stimulation and do not increase proliferation when activated in the presence of IL-2
|
• macrophage phagocytosis of bacteria is impaired by more than half
|
• neutrophils have a 3-fold decrease in their ability to phagocytose fluorescent-conjugated beads and bacteria in response to MLP stimulation
|
• thymi are under developed and lack a clear cortical/medullary architecture
|
• thymus numbers are reduced by 30-fold
|
• spleen hyperplasia occurs in these mice even though lymphoid cells are depleted, because of marked proliferation of myeloid and erythroid progenitors
|
• CFU-GM and CFU-GEMM progenitors are decreased in the bone marrow by a third to a half but are dramatically increased in the peripheral blood
|
• mutant bone marrow cells poorly reconstitute the thymi of immunideficient hosts with low numbers of mature T cells resulting in the periphery
• in these same recipient mice, mature B cells fail to develop unless recipient animals are also lethally irradiated in which case low numbers of B cells are found in the periphery
|
• the generation in vitro of Th17 T cells from mutant nave CD4+ T cells is enhanced compared to controls
|
• the percentage of double negative thymocytes is increased more than five fold as alphabeta T cell development is delayed at the DN3 to DN4 transition
|
• the percentage of double positive thymocytes is decreased as alphabeta T cell development is impaired at the double negative stage
|
• marked proliferation of myeloid and erythroid progenitors in the spleen is indicative of extramedullary hemopoiesis
• splenocytes have almost a 5-fold increase in the percentage of (Lin-Sca1+cKit+ hematopoietic stem cells
|
• the abnormal RBC shapes and lower MCV and hemocrit are all indicative of hypochromic microcytic anemia
|
• BFU-E progenitors are decreased in the bone marrow by a third to a half but are dramatically increased in the peripheral blood
|
• hematocrit is reduced by more than a third
|
• MCV is reduced around a third compared to controls
|
• acanthocytes (thorny red blood cells) are observed in the blood
|
• dacryocytes (tear-shaped red blood cells) are observed in the blood
|
• keratocytes (horned-shaped cells), dacryocytes (tear-shaped cells) and acanthocytes (thorny cells) are all observed in the blood
|
• RBC fragments are observed in the blood
|
• the ratio of FoxP3+CD4+ T cells to FoxP3-CD4+ T cells is enhanced in these mice both in the thymus and in the spleen
|
• lymphocytes numbers are decreased about 3.5-fold in the blood
|
• B cell numbers in the periphery are reduced by at least 75%
|
• CD4+ T cell numbers are decreased in the thymus and in the periphery by at least 75%
|
• CD8+ T cell numbers are decreased in the thymus and in the periphery by at least 75%
|
• gamma-delta T cell numbers are reduced in the thymus by 6-fold and in the spleen by 3-fold
|
• white blood cell count in the blood is increased about 2- to 2.5- fold
|
• neutrophil numbers are increased 25-fold in the blood
|
• the number of reticulocytes is greatly increased
|
• RBC are more sensitive to changes in osmolarity with more than double the percentage of cells lysing at 0.47% and 0.26% NaCl than wild-type
|
cellular
• neutrophils fail to migrate efficiently across a filter in response to different concentrations of the chemoattractant MLP
• neutrophils have defects in actin polymerization near the leading edge of cellular membranes
|
• T cells have reduced proliferation in response to CD3 and CD28 stimulation and do not increase proliferation when activated in the presence of IL-2
|
• macrophage phagocytosis of bacteria is impaired by more than half
|
• neutrophils have a 3-fold decrease in their ability to phagocytose fluorescent-conjugated beads and bacteria in response to MLP stimulation
|
endocrine/exocrine glands
• thymi are under developed and lack a clear cortical/medullary architecture
|
• thymus numbers are reduced by 30-fold
|