Phenotypes associated with this allele

• Allele Symbol: Gt(ROSA)26Sor^{tm1(CAG-STAT5B*N642H,-EGFP)Biat}
• Allele Name: targeted mutation 1, Biomodels Austria
• Allele ID: MGI:8259352
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gt(ROSA)26Sor^tm1(CAG-STAT5B*N642H,-EGFP)Biat/Gt(ROSA)26Sor^tm1(CAG-STAT5B*N642H,-EGFP)Biat Tg(Ncr1-icre)265Sxl/0	involves: C57BL/6N * C57BL/6NTac	MGI:8259757
cn2	Gt(ROSA)26Sor^tm1(CAG-STAT5B*N642H,-EGFP)Biat/Gt(ROSA)26Sor^+ Commd10^Tg(Vav1-icre)A2Kio/Commd10^+	involves: C57BL/6NTac * C57BL/10 * CBA/Ca	MGI:8259754

Genotype
MGI:8259757

cn1

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-STAT5B*N642H,-EGFP)Biat}/Gt(ROSA)26Sor^{tm1(CAG-STAT5B*N642H,-EGFP)Biat}; Tg(Ncr1-icre)265Sxl/0
• Genetic Background: involves: C57BL/6N * C57BL/6NTac

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

hematopoietic system

abnormal NK cell morphology ( J:350923 )

• levels of granzyme B and perforin are enhanced in NK cells

increased NK cell number ( J:350923 )

• mice show increased NK-cell numbers in blood, spleen, and bone marrow

• an expansion of NK cells is already detectable in the blood as early as 4 weeks of age

• NK cells are the predominantly expanded cell type in the spleen of 5 of 8 diseased mice

increased mature NK cell number ( J:350923 )

• mice show more mature NK cells in the bone morrow and spleen than controls

abnormal NK cell physiology ( J:350923 )

• splenic NK cells show reduced apoptosis ex vivo

immune system

abnormal NK cell morphology ( J:350923 )

• levels of granzyme B and perforin are enhanced in NK cells

increased NK cell number ( J:350923 )

• mice show increased NK-cell numbers in blood, spleen, and bone marrow

• an expansion of NK cells is already detectable in the blood as early as 4 weeks of age

• NK cells are the predominantly expanded cell type in the spleen of 5 of 8 diseased mice

increased mature NK cell number ( J:350923 )

• mice show more mature NK cells in the bone morrow and spleen than controls

abnormal NK cell physiology ( J:350923 )

• splenic NK cells show reduced apoptosis ex vivo

neoplasm

increased leukemia incidence ( J:350923 )

• 8 of 24 (approximately 33%) of mice develop NK-cell leukemia within 17 months; mice display an NK-large granular lymphocytic leukemia (NK-LGLL) that progresses to an aggressive leukemia with age, suffer from weight loss, splenomegaly, and expansion of EGFP+ cells in various organs, including spleen, liver, bone marrow, and blood

• NK cells are the predominantly expanded cell type in the spleen of 5 of 8 diseased mice

• transplantation of mutant splenic cells into immunodeficient NOD scid gamma (NSG) recipients, results in initiation of a fast-progressing leukemia in all recipient mice, with weight loss, hepatosplenomegaly, anemia and multiple organ infiltration and a leukemia with NK-cell phenotype is seen in about 70% of recipients

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
aggressive NK-cell leukemia		DOID:1035		J:350923

Genotype
MGI:8259754

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-STAT5B*N642H,-EGFP)Biat}/Gt(ROSA)26Sor⁺; Commd10^{Tg(Vav1-icre)A2Kio}/Commd10⁺
• Genetic Background: involves: C57BL/6NTac * C57BL/10 * CBA/Ca

mortality/aging

premature death ( J:350923 )

• upon aging, all mice develop a hematopoietic malignancy with a median survival of 186 days

growth/size/body

weight loss ( J:350923 )

• leukemic mice show reduced body weight

enlarged spleen ( J:350923 )

• mice show splenomegaly at 8 weeks of age, with expanded myeloid and B-cell compartments

hematopoietic system

enlarged spleen ( J:350923 )

• mice show splenomegaly at 8 weeks of age, with expanded myeloid and B-cell compartments

abnormal bone marrow cell morphology/development ( J:350923 )

• bone marrow of 8-week-old mice shows reduced numbers of erythroid (Ter119+) and NK cells (CD3-NK1.1+) and increased numbers of T cells (CD3+CD4+ or CD3+CD8+)

increased bone marrow cell number ( J:350923 )

• 8-week-old mice exhibit elevated bone marrow cellularity

decreased erythroid progenitor cell number ( J:350923 )

• numbers of erythroid (Ter119+) cells are reduced in the bone marrow of 8-week-old mice

decreased NK cell number ( J:350923 )

• numbers of NK cells (CD3-NK1.1+) are reduced in the bone marrow of 8-week-old mice

decreased CD4-positive, alpha-beta T cell number ( J:350923 )

• peripheral blood lacks any significant alterations, except for a decrease in the frequency of CD4+ T cells

increased hematopoietic cell number ( J:350923 )

• mice show elevated numbers of mature hematopoietic cell types in spleen, blood, and lymph nodes, but not in the bone marrow

• cell numbers are elevated in all lineages and no cell type is dominantly expanded

increased B cell number ( J:350923 )

• numbers of B cells (CD19+) are increased in the bone marrow of 8-week-old mice

increased T cell number ( J:350923 )

• numbers of T cells (CD3+CD4+ or CD3+CD8+) are increased in the bone marrow of 8-week-old mice

increased hematopoietic stem cell number ( J:350923 )

• 8-week-old mice exhibit an enlarged hematopoietic stem cell pool under homeostatic conditions

immune system

enlarged spleen ( J:350923 )

• mice show splenomegaly at 8 weeks of age, with expanded myeloid and B-cell compartments

increased B cell number ( J:350923 )

• numbers of B cells (CD19+) are increased in the bone marrow of 8-week-old mice

decreased NK cell number ( J:350923 )

• numbers of NK cells (CD3-NK1.1+) are reduced in the bone marrow of 8-week-old mice

decreased CD4-positive, alpha-beta T cell number ( J:350923 )

• peripheral blood lacks any significant alterations, except for a decrease in the frequency of CD4+ T cells

increased T cell number ( J:350923 )

• numbers of T cells (CD3+CD4+ or CD3+CD8+) are increased in the bone marrow of 8-week-old mice

enlarged lymph nodes ( J:350923 )

neoplasm

increased leukemia incidence ( J:350923 )

• mice develop slowly progressing CD4+, CD8+ T- or NKT-cell leukemia, as indicated by blood smears of diseased mice which show leukemic blast-like cells

• leukemic T/NKT cells expand upon transplantation into immunodeficient NOD scid gamma (NSG) recipients, infiltrating the bone marrow, spleen and lungs indicating the development of leukemia

• however, mice do not develop NK-cell leukemia

• mice show immune cell infiltration in the lungs which is associated with disruption of the regular lung architecture