Analysis Tools
mortality/aging
|
• median survival is 16 months of age
|
neoplasm
|
• mutants develop an aggressive, fatal T-cell malignancy
• majority of lymphomas have clinical, morphological, and immunophenotypical features of peripheral T-cell lymphoma (PTCL) and are derived from activated T cells
• tumors exhibit clonal Tcrb rearrangements
• peripheral T-cell lymphoma is characterized by widespread infiltration of parenchymal organs with malignant CD4+ cells
• cells from mutant tumors injected into Prkdcscid mice form subcutaneous tumors
|
behavior/neurological
|
• develops around 10 months of age indicating signs of disease
|
integument
ruffled hair
(
J:189197
)
|
• develops around 10 months of age indicating signs of disease
|
respiratory system
|
• ascites or pleural effusions are seen occasionally at 10 months of age
|
immune system
|
• increase in CD4+ T cell proliferation in the thymus
|
|
• thymus shows an increase in the number of C8 single positive cells, decrease in the number of double-positive T cells, an increase in the proportion of mature T cells (CD69-TCRb+), and an increase in the number of B220+ B cells infiltrating the thymus
|
|
• thymus exhibits a narrower cortex
|
|
• thymus shows a less distinct corticomedullary junction
|
|
• thymus exhibits a more expansive medulla
|
|
• mutants develop an aggressive, fatal T-cell malignancy
• majority of lymphomas have clinical, morphological, and immunophenotypical features of peripheral T-cell lymphoma (PTCL) and are derived from activated T cells
• tumors exhibit clonal Tcrb rearrangements
• peripheral T-cell lymphoma is characterized by widespread infiltration of parenchymal organs with malignant CD4+ cells
• cells from mutant tumors injected into Prkdcscid mice form subcutaneous tumors
|
|
• splenomegaly at 10 months of age
• however, mutants typically have a normal sized thymus
|
|
• impaired T cell development
|
|
• 3- to 4-fold increase in the percentage of both CD4 and CD8 effector memory T cells (CD62L-CD44+) in peripheral blood
|
|
• number of CD8 single positive cells is increased in the thymus
|
|
• 3- to 4-fold increase in the percentage of both CD4 and CD8 effector memory T cells (CD62L-CD44+) in peripheral blood
|
|
• white blood cell count is decreased by nearly 2-fold at 2 months of age
• lymphopenia is cell autonomous and not dependent on host-derived stromal cells
• however, no differences in the absolute numbers of granulocytes, monocytes, red blood cells, and platelets, in the number of bone marrow colony-forming units or the replating potential of these colonies, and no differences in the proportion of B-cell precursors or common lymphoid progenitors
|
|
• 2.6-fold decrease in circulating lymphocytes
|
|
• number of CD4+CD8+ cells in the thymus is decreased
|
|
• in peripheral blood
|
|
• in peripheral blood
|
|
• hypergammaglobulinemia, with 3 of 4 mutants having serum IgG levels higher than controls
|
|
• several proinflammatory chemokines, cytokines, and complement, such as Ccl11, Ccl20, Ccl8, Cxcr5, Cxcl1, Il-7, and C4b, are increased in tumor samples
|
|
• lymphadenopathy at 10 months of age
|
|
• spleen, liver, and lungs are infiltrated with sheets of CD3+ T cells interspersed with B220+ B cells
• C-reactive protein, a serum marker for inflammation, is elevated in 3 of 5 clinically healthy mutants that show no signs of illness, indicating systemic inflammation preceding the onset of T-cell lymphoma
|
homeostasis/metabolism
|
• ascites or pleural effusions are seen occasionally at 10 months of age
|
|
• several proinflammatory chemokines, cytokines, and complement, such as Ccl11, Ccl20, Ccl8, Cxcr5, Cxcl1, Il-7, and C4b, are increased in tumor samples
|
hematopoietic system
|
• increase in CD4+ T cell proliferation in the thymus
|
|
• thymus shows an increase in the number of C8 single positive cells, decrease in the number of double-positive T cells, an increase in the proportion of mature T cells (CD69-TCRb+), and an increase in the number of B220+ B cells infiltrating the thymus
|
|
• thymus exhibits a narrower cortex
|
|
• thymus shows a less distinct corticomedullary junction
|
|
• thymus exhibits a more expansive medulla
|
|
• mutants develop an aggressive, fatal T-cell malignancy
• majority of lymphomas have clinical, morphological, and immunophenotypical features of peripheral T-cell lymphoma (PTCL) and are derived from activated T cells
• tumors exhibit clonal Tcrb rearrangements
• peripheral T-cell lymphoma is characterized by widespread infiltration of parenchymal organs with malignant CD4+ cells
• cells from mutant tumors injected into Prkdcscid mice form subcutaneous tumors
|
|
• splenomegaly at 10 months of age
• however, mutants typically have a normal sized thymus
|
|
• impaired T cell development
|
|
• 3- to 4-fold increase in the percentage of both CD4 and CD8 effector memory T cells (CD62L-CD44+) in peripheral blood
|
|
• number of CD8 single positive cells is increased in the thymus
|
|
• 3- to 4-fold increase in the percentage of both CD4 and CD8 effector memory T cells (CD62L-CD44+) in peripheral blood
|
|
• white blood cell count is decreased by nearly 2-fold at 2 months of age
• lymphopenia is cell autonomous and not dependent on host-derived stromal cells
• however, no differences in the absolute numbers of granulocytes, monocytes, red blood cells, and platelets, in the number of bone marrow colony-forming units or the replating potential of these colonies, and no differences in the proportion of B-cell precursors or common lymphoid progenitors
|
|
• 2.6-fold decrease in circulating lymphocytes
|
|
• number of CD4+CD8+ cells in the thymus is decreased
|
|
• in peripheral blood
|
|
• in peripheral blood
|
|
• hypergammaglobulinemia, with 3 of 4 mutants having serum IgG levels higher than controls
|
endocrine/exocrine glands
|
• thymus shows an increase in the number of C8 single positive cells, decrease in the number of double-positive T cells, an increase in the proportion of mature T cells (CD69-TCRb+), and an increase in the number of B220+ B cells infiltrating the thymus
|
|
• thymus exhibits a narrower cortex
|
|
• thymus shows a less distinct corticomedullary junction
|
|
• thymus exhibits a more expansive medulla
|
|
• mutants develop an aggressive, fatal T-cell malignancy
• majority of lymphomas have clinical, morphological, and immunophenotypical features of peripheral T-cell lymphoma (PTCL) and are derived from activated T cells
• tumors exhibit clonal Tcrb rearrangements
• peripheral T-cell lymphoma is characterized by widespread infiltration of parenchymal organs with malignant CD4+ cells
• cells from mutant tumors injected into Prkdcscid mice form subcutaneous tumors
|
growth/size/body
|
• splenomegaly at 10 months of age
• however, mutants typically have a normal sized thymus
|
cellular
|
• increase in CD4+ T cell proliferation in the thymus
|
