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Phenotypes Associated with This Genotype
Genotype
MGI:5792659
Allelic
Composition
Ifngtm1.1Hayg/Ifngtm1.1Hayg
Genetic
Background
Not Specified
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ifngtm1.1Hayg mutation (0 available); any Ifng mutation (36 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• thymus shows structural damage and atrophy

hematopoietic system
• thymus shows structural damage and atrophy
• 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
• disruption in early B-cell differentiation, with a reduction in pre-B cells
• mice develop aplastic anemia
• bone marrow transplantation from wild-type mice into mutant mice reverses the aplastic anemia phenotype
• differentiation of multipotent progenitors to myeloid progenitors and differentiation of red blood cells and B cells is inhibited
• total number of burst-forming unit erythroid, colony-forming unit-granulocyte, -erythrocyte, -macrophage, and megakaryocyte, CFU-granulocyte, -macrophage, -megakaryocyte, and granulocyte progenitors are lower
• 4-fold decrease in the numbers of common myeloid progenitors
• 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
• total bone marrow cellularity is about 25% that of wild-type mice
• 4-fold decrease in the numbers of granulocyte/monocyte progenitors (GMP)
• bone marrow shows a decrease in megakaryocytes at 3 weeks of age
• total number of burst-forming unit erythroid number is lower
• 2-fold increase in the percentage of proerythorblasts in the bone marrow
• 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
• low red blood cell counts
• 2-fold decrease in the percentage of mature erythrocytes in the bone marrow
• 2-fold increase in the percentage of immature erythrocytes in the bone marrow
• low platelet counts
• treatment of 3 week old mice with an IFN-gamma-neutralizing antibody restores platelet levels
• slight expansion in four TCR Vbeta subfamilies in CD4 T cells (27%) and two Vbeta subfamilies in CD8 T cells (17%)
• low white blood cell counts
• the absolute cell numbers of pre-B cells and mature B cells is reduced about 8-fold
• 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
• peripheral blood pancytopenia
• 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
• 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
• 8-fold decrease in the numbers of megakaryocyte/erythrocyte progenitors (MEPs)
• spleen shows structural damage and atrophy
• 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
• 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
• 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 shows structural damage and atrophy
• disruption in early B-cell differentiation, with a reduction in pre-B cells
• slight expansion in four TCR Vbeta subfamilies in CD4 T cells (27%) and two Vbeta subfamilies in CD8 T cells (17%)
• low white blood cell counts
• the absolute cell numbers of pre-B cells and mature B cells is reduced about 8-fold
• 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 shows structural damage and atrophy
• spleen and lymph node T cells show hyporesponsiveness after a mixed lymphocyte reaction
• bone marrow T cells produce lower cytokine levels after TCR stimulation
• 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
• serum levels of hematopoietic cytokines, Flt3 ligand, stem cell factor, IL-2, and erythropoietin are increased 2-, 1.5-, 3-, and 7-fold, respectively
• 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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
01/14/2020
MGI 6.14
The Jackson Laboratory