neoplasm
• mice develop acute T-cell lymphoblastic leukemia, with 90% of mice becoming sick at 4-8 months of age
• nearly 100% of cells in the spleen express Ki-67, indicating a very high proliferation index that is characteristic of an aggressive, rapidly growing leukemia
• the majority of splenic T cells exhibit BrdU incorporation, indicating robust proliferation
• the majority of malignant cells are immature T-cells expressing TdT and lacking NK1.1
|
hematopoietic system
• nearly all mice develop enlarged spleens
|
• mutants have essentially no circulating B cells (0.6% vs. 12.4% in wild-type)
|
• blood contains fewer T cells (17.1%) than in wild-type mice (65.3%)
|
• marked expansion of the T-cell population in the spleen of 4-8 month old mice
• 82.7% of bone marrow lymphocytes are T cells compared to 9.1% in wild-type littermates
|
• spleens exhibit a greater cell density, with increased CD3+ T cells and mononuclear cells
|
• about 3-fold decrease in serum IgG1 levels
|
• 3.5-fold decrease in serum IgG2a levels
|
• 3.5-fold decrease in serum IgG2b levels
|
• 3.5-fold decrease in serum IgG3 levels
|
homeostasis/metabolism
• 6-fold higher serum levels of IL-6
|
• 6-fold higher serum levels of IL-6
|
immune system
• nearly all mice develop enlarged spleens
|
• mutants have essentially no circulating B cells (0.6% vs. 12.4% in wild-type)
|
• blood contains fewer T cells (17.1%) than in wild-type mice (65.3%)
|
• marked expansion of the T-cell population in the spleen of 4-8 month old mice
• 82.7% of bone marrow lymphocytes are T cells compared to 9.1% in wild-type littermates
|
• spleens exhibit a greater cell density, with increased CD3+ T cells and mononuclear cells
|
• about 3-fold decrease in serum IgG1 levels
|
• 3.5-fold decrease in serum IgG2a levels
|
• 3.5-fold decrease in serum IgG2b levels
|
• 3.5-fold decrease in serum IgG3 levels
|
• 6-fold higher serum levels of IL-6
|
• 6-fold higher serum levels of IL-6
|
• nearly all mice develop multiple enlarged lymph nodes
|
• the ability of mice to mount an immune response to an antigen KHL is reduced by about 3-fold
|
integument
• 30% of mice exhibit severe alopecia associated with a maculopapular skin lesion
|
• the dermis is expanded by a broadband infiltrate of mononuclear cells and involves the subcutaneous adipose tissue
|
skin lesions
(
J:233225
)
• maculopapular skin lesions
|
growth/size/body
• nearly all mice develop enlarged spleens
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
acute lymphoblastic leukemia | DOID:9952 |
OMIM:247640 OMIM:613065 |
J:233225 |