Phenotypes Associated with This Genotype

Genotype
MGI:6164043

• Allelic Composition: Tg(Vav1-STAT5B*N642H)726Biat/0
• Genetic Background: C57BL/6NCrl-Tg(Vav1-STAT5B*N642H)726Biat

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

mortality/aging

premature death ( J:257519 )

• death occurs between 40 and 100 days of age

hematopoietic system

increased T cell proliferation ( J:257519 )

• high numbers of proliferating T cells that heavily infiltrate peripheral organs

• the JAK inhibitors ruxolitinib and tofacitinib reduce cell viability

• T cells are more sensitive to the duel-specific JAK and Aurora kinase inhibitor AT9283

abnormal bone marrow cell morphology/development ( J:257519 )

• expansion of CD3+ T cells, but not CD19+ B cells in the bone marrow

• increase in the percentage of CD11b+Gr1+ cells in the bone marrow

increased common myeloid progenitor cell number ( J:257519 )

• numbers of myeloid progenitor cells (MPCs) are elevated

increased common lymphocyte progenitor cell number ( J:257519 )

• numbers of common lymphoid progenitors (CLPs) are elevated, with mice having 3x more CLPs than wild-type mice

abnormal effector T cell number ( J:257519 )

• percentage of cells expressing markers for effector memory T cells is elevated

increased leukocyte cell number ( J:257519 )

• approximate 20-fold increase in white blood cell counts

increased CD4-positive, alpha-beta T cell number ( J:257519 )

• numbers of CD4+ T cells are moderately increased

increased CD8-positive, alpha-beta T cell number ( J:257519 )

• expansion of CD8+ T cells, with T cell infiltration into peripheral organs

• CD8+ T cells are increased by 3-fold in the lymph nodes

• 50% of diseased CD8+ T cells express markers of central memory T cells

increased hematopoietic stem cell number ( J:257519 )

• increase in numbers of progenitor cells throughout all early hematopoietic compartments, including lineage-Sca1+c-Kit+ cells (LSKs), long-term hematopoietic stem cells (LT-HSCs), short-term HSCs (ST-HSCs) and multipotent progenitors (MPPs; CD150+CD48-, CD150+CD48+, CD150-CD48+ fractions)

abnormal spleen morphology ( J:257519 )

• mild expansion of other hematopoietic cells such as CD19+ B cells, CD4+ T cells, and CD11b+Gr1+ myeloid cells in the spleen

enlarged spleen ( J:257519 )

• high numbers of proliferating T cells are associated with splenomegaly

immune system

increased T cell proliferation ( J:257519 )

• high numbers of proliferating T cells that heavily infiltrate peripheral organs

• the JAK inhibitors ruxolitinib and tofacitinib reduce cell viability

• T cells are more sensitive to the duel-specific JAK and Aurora kinase inhibitor AT9283

abnormal effector T cell number ( J:257519 )

• percentage of cells expressing markers for effector memory T cells is elevated

increased leukocyte cell number ( J:257519 )

• approximate 20-fold increase in white blood cell counts

increased CD4-positive, alpha-beta T cell number ( J:257519 )

• numbers of CD4+ T cells are moderately increased

increased CD8-positive, alpha-beta T cell number ( J:257519 )

• expansion of CD8+ T cells, with T cell infiltration into peripheral organs

• CD8+ T cells are increased by 3-fold in the lymph nodes

• 50% of diseased CD8+ T cells express markers of central memory T cells

abnormal spleen morphology ( J:257519 )

• mild expansion of other hematopoietic cells such as CD19+ B cells, CD4+ T cells, and CD11b+Gr1+ myeloid cells in the spleen

enlarged spleen ( J:257519 )

• high numbers of proliferating T cells are associated with splenomegaly

abnormal lymph node morphology ( J:257519 )

• the percentage, but not the total number, of CD19+ B cells is reduced in the lymph nodes

neoplasm

increased leukemia incidence ( J:257519 )

• mice rapidly develop malignant disease, either leukemia or lymphoma characterized by highly proliferative and invasive CD8+ T cells

• leukemic cells express surface makers indicative of mature T cells with an activated phenotype

increased lymphoma incidence ( J:257519 )

• mice rapidly develop malignant disease, either leukemia or lymphoma characterized by highly proliferative and invasive CD8+ T cells

respiratory system

abnormal respiratory system physiology ( J:257519 )

• proliferating T cells heavily infiltrate peripheral organs, leading to fatal pulmonary obstruction

cellular

increased T cell proliferation ( J:257519 )

• high numbers of proliferating T cells that heavily infiltrate peripheral organs

• the JAK inhibitors ruxolitinib and tofacitinib reduce cell viability

• T cells are more sensitive to the duel-specific JAK and Aurora kinase inhibitor AT9283

growth/size/body

enlarged spleen ( J:257519 )

• high numbers of proliferating T cells are associated with splenomegaly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
leukemia		DOID:1240		J:257519
lymphoma		DOID:0060058		J:257519