Phenotypes Associated with This Genotype

Genotype
MGI:5792659

• Allelic Composition: Ifng^tm1.1Hayg/Ifng^tm1.1Hayg
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

endocrine/exocrine glands

thymus atrophy ( J:220784 )

• thymus shows structural damage and atrophy

hematopoietic system

thymus atrophy ( J:220784 )

• thymus shows structural damage and atrophy

abnormal erythropoiesis ( J:220784 )

• immature erythrocytes fail to differentiate into mature cells, resulting in a severe 9-fold decrease in the total erythroid cell output

• treatment of 3 week old mice with an IFN-gamma-neutralizing antibody restores erythropoiesis

• bone marrow transplantation from wild-type mice into mutant mice resolves the blocks in erythropoiesis

abnormal B cell differentiation ( J:220784 )

• disruption in early B-cell differentiation, with a reduction in pre-B cells

anemia ( J:220784 )

• mice develop aplastic anemia

• bone marrow transplantation from wild-type mice into mutant mice reverses the aplastic anemia phenotype

impaired hematopoiesis ( J:220784 )

• differentiation of multipotent progenitors to myeloid progenitors and differentiation of red blood cells and B cells is inhibited

abnormal bone marrow cell morphology/development ( J:220784 )

• total number of burst-forming unit erythroid, colony-forming unit-granulocyte, -erythrocyte, -macrophage, and megakaryocyte, CFU-granulocyte, -macrophage, -megakaryocyte, and granulocyte progenitors are lower

decreased common myeloid progenitor cell number ( J:220784 )

• 4-fold decrease in the numbers of common myeloid progenitors

decreased myeloid cell number in bone marrow ( J:220784 )

• bone marrow cellularity is further decreased with loss of myeloid cells at week 6

• 3-fold reduction in the total number of myeloid cells in the bone marrow

decreased bone marrow cell number ( J:220784 )

• total bone marrow cellularity is about 25% that of wild-type mice

decreased granulocyte monocyte progenitor cell number ( J:220784 )

• 4-fold decrease in the numbers of granulocyte/monocyte progenitors (GMP)

decreased megakaryocyte cell number ( J:220784 )

• bone marrow shows a decrease in megakaryocytes at 3 weeks of age

decreased erythroid progenitor cell number ( J:220784 )

• total number of burst-forming unit erythroid number is lower

abnormal proerythroblast morphology ( J:220784 )

• 2-fold increase in the percentage of proerythorblasts in the bone marrow

increased erythroblast number ( J:220784 )

• 2-fold increase in the percentage of polychromatophilic erythroblasts in the bone marrow

• 2-fold decrease in the percentage of orthochromatophilic erythroblasts in the bone marrow

decreased erythrocyte cell number ( J:220784 )

• low red blood cell counts

• 2-fold decrease in the percentage of mature erythrocytes in the bone marrow

increased nucleated erythrocyte cell number ( J:220784 )

• 2-fold increase in the percentage of immature erythrocytes in the bone marrow

thrombocytopenia ( J:220784 )

• low platelet counts

• treatment of 3 week old mice with an IFN-gamma-neutralizing antibody restores platelet levels

increased T cell number ( J:220784 )

• slight expansion in four TCR Vbeta subfamilies in CD4 T cells (27%) and two Vbeta subfamilies in CD8 T cells (17%)

decreased leukocyte cell number ( J:220784 )

• low white blood cell counts

decreased mature B cell number ( J:220784 )

• the absolute cell numbers of pre-B cells and mature B cells is reduced about 8-fold

decreased pre-B cell number ( J:220784 )

• 2-fold reduction in the percentage of pre-B cells, indicating a disruption in early B-cell differentiation

• the absolute cell numbers of pre-B and mature B cells is reduced about 8-fold

pancytopenia ( J:220784 )

• peripheral blood pancytopenia

abnormal hematopoietic stem cell morphology ( J:220784 )

• proliferation of the LSK population is 2-fold higher than in wild-type mice

• proliferation of the KL population is 30% lower than in wild-type mice

• bone marrow transplantation from wild-type mice into mutant mice restores the hematopoietic progenitor and stem cell composition

• treatment of 3 week old mice with an IFN-gamma-neutralizing antibody reverses hematopoietic progenitor and stem cell composition

increased hematopoietic stem cell number ( J:220784 )

• 2.5-fold increase in long-term hematopoietic stem cells

• however, no differences in the numbers of short-term hematopoietic stem cells, multipotent progenitors, and common lymphoid progenitors are seen

decreased megakaryocyte-erythroid progenitor cell number ( J:220784 )

• 8-fold decrease in the numbers of megakaryocyte/erythrocyte progenitors (MEPs)

spleen atrophy ( J:220784 )

• spleen shows structural damage and atrophy

abnormal T cell activation ( J:220784 )

• spleen and lymph node T cells show hyporesponsiveness after a mixed lymphocyte reaction

• bone marrow T cells produce lower cytokine levels after TCR stimulation

homeostasis/metabolism

abnormal cytokine level ( J:220784 )

• cytokine levels (IL-10, IL-17a, IFN-gamma, IL-4, IL-2, and IL-6) expressed by bone marrow T cells after TCR stimulation are lower

abnormal circulating cytokine level ( J:220784 )

• serum levels of hematopoietic cytokines, Flt3 ligand, stem cell factor, IL-2, and erythropoietin are increased 2-, 1.5-, 3-, and 7-fold, respectively

immune system

thymus atrophy ( J:220784 )

• thymus shows structural damage and atrophy

abnormal B cell differentiation ( J:220784 )

• disruption in early B-cell differentiation, with a reduction in pre-B cells

increased T cell number ( J:220784 )

• slight expansion in four TCR Vbeta subfamilies in CD4 T cells (27%) and two Vbeta subfamilies in CD8 T cells (17%)

decreased leukocyte cell number ( J:220784 )

• low white blood cell counts

decreased mature B cell number ( J:220784 )

• the absolute cell numbers of pre-B cells and mature B cells is reduced about 8-fold

decreased pre-B cell number ( J:220784 )

• 2-fold reduction in the percentage of pre-B cells, indicating a disruption in early B-cell differentiation

• the absolute cell numbers of pre-B and mature B cells is reduced about 8-fold

spleen atrophy ( J:220784 )

• spleen shows structural damage and atrophy

abnormal T cell activation ( J:220784 )

• spleen and lymph node T cells show hyporesponsiveness after a mixed lymphocyte reaction

• bone marrow T cells produce lower cytokine levels after TCR stimulation

abnormal cytokine level ( J:220784 )

• cytokine levels (IL-10, IL-17a, IFN-gamma, IL-4, IL-2, and IL-6) expressed by bone marrow T cells after TCR stimulation are lower

abnormal circulating cytokine level ( J:220784 )

• serum levels of hematopoietic cytokines, Flt3 ligand, stem cell factor, IL-2, and erythropoietin are increased 2-, 1.5-, 3-, and 7-fold, respectively

abnormal lymph node morphology ( J:220784 )

• lymph nodes show structural damage and atrophy

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
aplastic anemia		DOID:12449	OMIM:609135	J:220784