Phenotypes Associated with This Genotype

Genotype
MGI:5788543

• Allelic Composition: Tg(Igh-HMGA2)#Cro/0
• Genetic Background: FVB/N-Tg(Igh-HMGA2)#Cro

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

neoplasm

increased T cell acute lymphoblastic leukemia incidence ( J:233225 )

• 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

enlarged spleen ( J:233225 )

• nearly all mice develop enlarged spleens

decreased B cell number ( J:233225 )

• mutants have essentially no circulating B cells (0.6% vs. 12.4% in wild-type)

decreased T cell number ( J:233225 )

• blood contains fewer T cells (17.1%) than in wild-type mice (65.3%)

increased T cell number ( J:233225 )

• 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

abnormal splenic cell ratio ( J:233225 )

• spleens exhibit a greater cell density, with increased CD3+ T cells and mononuclear cells

decreased IgG1 level ( J:233225 )

• about 3-fold decrease in serum IgG1 levels

decreased IgG2a level ( J:233225 )

• 3.5-fold decrease in serum IgG2a levels

decreased IgG2b level ( J:233225 )

• 3.5-fold decrease in serum IgG2b levels

decreased IgG3 level ( J:233225 )

• 3.5-fold decrease in serum IgG3 levels

homeostasis/metabolism

increased circulating interleukin-6 level ( J:233225 )

• 6-fold higher serum levels of IL-6

increased circulating tumor necrosis factor level ( J:233225 )

• 6-fold higher serum levels of IL-6

immune system

enlarged spleen ( J:233225 )

• nearly all mice develop enlarged spleens

decreased B cell number ( J:233225 )

• mutants have essentially no circulating B cells (0.6% vs. 12.4% in wild-type)

decreased T cell number ( J:233225 )

• blood contains fewer T cells (17.1%) than in wild-type mice (65.3%)

increased T cell number ( J:233225 )

• 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

abnormal splenic cell ratio ( J:233225 )

• spleens exhibit a greater cell density, with increased CD3+ T cells and mononuclear cells

decreased IgG1 level ( J:233225 )

• about 3-fold decrease in serum IgG1 levels

decreased IgG2a level ( J:233225 )

• 3.5-fold decrease in serum IgG2a levels

decreased IgG2b level ( J:233225 )

• 3.5-fold decrease in serum IgG2b levels

decreased IgG3 level ( J:233225 )

• 3.5-fold decrease in serum IgG3 levels

increased circulating interleukin-6 level ( J:233225 )

• 6-fold higher serum levels of IL-6

increased circulating tumor necrosis factor level ( J:233225 )

• 6-fold higher serum levels of IL-6

enlarged lymph nodes ( J:233225 )

• nearly all mice develop multiple enlarged lymph nodes

decreased response to antigen ( J:233225 )

• the ability of mice to mount an immune response to an antigen KHL is reduced by about 3-fold

integument

alopecia ( J:233225 )

• 30% of mice exhibit severe alopecia associated with a maculopapular skin lesion

abnormal dermal layer morphology ( J:233225 )

• 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

enlarged spleen ( J:233225 )

• 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