Phenotypes associated with this allele

• Allele Symbol: Irf8^tm1Hor
• Allele Name: targeted mutation 1, Ivan Horak
• Allele ID: MGI:1926332
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Irf8^tm1Hor/Irf8^tm1Hor	B6.129P2-Irf8^tm1Hor	MGI:4939595
hm2	Irf8^tm1Hor/Irf8^tm1Hor	either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * C57BL/6)	MGI:2175074
hm3	Irf8^tm1Hor/Irf8^tm1Hor	involves: 129P2/OlaHsd * C57BL/6	MGI:5313306
ht4	Irf8^tm1Hor/Irf8^+	either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * C57BL/6)	MGI:2175075
cx5	Irf8^tm1Hor/Irf8^tm1Hor Irf4^tm1Mak/Irf4^tm1Mak	involves: 129P2/OlaHsd * C57BL/6	MGI:3584112
cx6	Id2^tm1Gtbz/Id2^tm1Gtbz Irf8^tm1Hor/Irf8^tm1Hor	involves: 129P2/OlaHsd * C57BL/6	MGI:5486202

Genotype
MGI:4939595

hm1

• Allelic Composition: Irf8^tm1Hor/Irf8^tm1Hor
• Genetic Background: B6.129P2-Irf8^tm1Hor

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

immune system

decreased follicular B cell number ( J:168923 )

increased B-1b cell number ( J:168923 )

increased marginal zone B cell number ( J:168923 )

hematopoietic system

decreased follicular B cell number ( J:168923 )

increased B-1b cell number ( J:168923 )

increased marginal zone B cell number ( J:168923 )

Genotype
MGI:2175074

hm2

• Allelic Composition: Irf8^tm1Hor/Irf8^tm1Hor
• Genetic Background: either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * C57BL/6)

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:36038 )

• 80% of mice infected with vacinia virus or lymphocytic choriomeningitis virus die within 10 to 20 days unlike wild-type mice that control the infection

premature death ( J:36038 )

• 33% of mice are moribund by 50 weeks of age with features indicating a transition to blast crisis

growth/size/body

hepatosplenomegaly ( J:36038 )

• mice develop hepatosplenomegaly with spleen weights of 500 to 2000 mg

increased spleen weight ( J:36038 )

• spleen weights of 500 to 2000 mg

spleen hyperplasia ( J:36038 )

immune system

hepatosplenomegaly ( J:36038 )

• mice develop hepatosplenomegaly with spleen weights of 500 to 2000 mg

increased spleen weight ( J:36038 )

• spleen weights of 500 to 2000 mg

spleen hyperplasia ( J:36038 )

decreased lymphocyte cell number ( J:36038 )

• in the bone marrow

decreased B cell number ( J:36038 )

• the relative frequency of B cells is decreased in the spleen

decreased T cell number ( J:36038 )

• the relative frequency of T cells is decreased in the spleen

increased leukocyte cell number ( J:36038 )

• 38.9+/-9.5 leukocytes per ul x10³ compared to 6.76+/-0.55 leukocytes per ul x10³ in wild-type mice

increased granulocyte number ( J:36038 )

• the frequency of granulocytes in the spleen, lymph node, peripheral blood and bone marrow is increased relative to in wild-type mice

• the frequency of granulocytes in the spleen and lymph nodes increases with age

increased lymphocyte cell number ( J:36038 )

• mice exhibit lymphocyte and plasma cells hyperplasia in Peyer's patches and the lamina propria

increased B cell number ( J:36038 )

• the frequency of B cells is increased in the lymph nodes

increased mature B cell number ( J:36038 )

• the relative frequency of B cells is decreased in the spleen

increased macrophage cell number ( J:36038 )

• the frequency of macrophage in the spleen, lymph node and bone marrow is increased relative to in wild-type mice

abnormal plasma cell number ( J:36038 )

• the frequency of plasma cells I reduced in the bone marrow while mice exhibit plasma cells hyperplasia in Peyer's patches and the lamina propria

increased spleen red pulp amount ( J:36038 )

increased immunoglobulin level ( J:36038 )

abnormal cytotoxic T cell physiology ( J:36038 )

• following infection with lymphocytic choriomeningitis virus strain WE, mice exhibit 40% mortality, a reduction in primary and absence of secondary cytotoxic lymphocyte response, and persistence of the virus in the liver, spleen and kidney

enlarged lymph nodes ( J:36038 )

• lymph nodes are enlarged 5-fold and are populated by neutrophilic granulocytes

decreased interferon-gamma secretion ( J:36038 )

• interferon-gamma production following stimulation with ConA is reduced 3-fold while production following stimulation with LPS is decreased more than 100-fold compared to in wild-type mice

increased susceptibility to Riboviria infection ( J:36038 )

• 80% of mice infected with vacinia virus or lymphocytic choriomeningitis virus die within 10 to 20 days unlike wild-type mice that control the infection

• cytotoxic T lymphocyte response is reduced 3- to 10-fold following infection with vesicular stomatitis virus and vacinia virus

• following infection with lymphocytic choriomeningitis virus strain WE, mice exhibit 40% mortality, a reduction in primary and absence of secondary cytotoxic lymphocyte response, and persistence of the virus in the liver, spleen and kidney

neoplasm

increased chronic myelocytic leukemia incidence ( J:36038 )

• all mice develop hematologic neoplasia resembling chronic myelogenous leukemia

• 33% of mice are moribund by 50 weeks of age with features indicating a transition to blast crisis

increased lymphoma incidence ( J:36038 )

hematopoietic system

hepatosplenomegaly ( J:36038 )

• mice develop hepatosplenomegaly with spleen weights of 500 to 2000 mg

increased spleen weight ( J:36038 )

• spleen weights of 500 to 2000 mg

spleen hyperplasia ( J:36038 )

abnormal erythropoiesis ( J:36038 )

• erythropoiesis is increased compared to in wild-type mice

increased bone marrow cell number ( J:36038 )

• bone marrows exhibit hypercellularity due to an increase in mature granulocytes and their precursors compared to in wild-type mice

abnormal megakaryocyte morphology ( J:36038 )

• mice exhibit increased proliferation of abnormal megakaryocytes

decreased lymphocyte cell number ( J:36038 )

• in the bone marrow

decreased B cell number ( J:36038 )

• the relative frequency of B cells is decreased in the spleen

decreased T cell number ( J:36038 )

• the relative frequency of T cells is decreased in the spleen

increased leukocyte cell number ( J:36038 )

• 38.9+/-9.5 leukocytes per ul x10³ compared to 6.76+/-0.55 leukocytes per ul x10³ in wild-type mice

increased granulocyte number ( J:36038 )

• the frequency of granulocytes in the spleen, lymph node, peripheral blood and bone marrow is increased relative to in wild-type mice

• the frequency of granulocytes in the spleen and lymph nodes increases with age

increased lymphocyte cell number ( J:36038 )

• mice exhibit lymphocyte and plasma cells hyperplasia in Peyer's patches and the lamina propria

increased B cell number ( J:36038 )

• the frequency of B cells is increased in the lymph nodes

increased mature B cell number ( J:36038 )

• the relative frequency of B cells is decreased in the spleen

increased macrophage cell number ( J:36038 )

• the frequency of macrophage in the spleen, lymph node and bone marrow is increased relative to in wild-type mice

abnormal plasma cell number ( J:36038 )

• the frequency of plasma cells I reduced in the bone marrow while mice exhibit plasma cells hyperplasia in Peyer's patches and the lamina propria

increased spleen red pulp amount ( J:36038 )

increased immunoglobulin level ( J:36038 )

abnormal cytotoxic T cell physiology ( J:36038 )

• following infection with lymphocytic choriomeningitis virus strain WE, mice exhibit 40% mortality, a reduction in primary and absence of secondary cytotoxic lymphocyte response, and persistence of the virus in the liver, spleen and kidney

liver/biliary system

hepatosplenomegaly ( J:36038 )

• mice develop hepatosplenomegaly with spleen weights of 500 to 2000 mg

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial chronic myelocytic leukemia-like syndrome		DOID:0060761	OMIM:600080	J:36038

Genotype
MGI:5313306

hm3

• Allelic Composition: Irf8^tm1Hor/Irf8^tm1Hor
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

abnormal humoral immune response ( J:181366 )

• coupling antigen to anti-Clec9a antibody fails to enhance antibody response

Genotype
MGI:2175075

ht4

• Allelic Composition: Irf8^tm1Hor/Irf8⁺
• Genetic Background: either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * C57BL/6)

mortality/aging

premature death ( J:36038 )

• 9% of mice are moribund by 50 weeks of age with features indicating a transition to blast crisis

neoplasm

increased chronic myelocytic leukemia incidence ( J:36038 )

• hematological neoplasia

• 9% of mice are moribund by 50 weeks of age with features indicating a transition to blast crisis

hematopoietic system

abnormal definitive hematopoiesis ( J:36038 )

• deranged hematopoiesis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial chronic myelocytic leukemia-like syndrome		DOID:0060761	OMIM:600080	J:36038

Genotype
MGI:3584112

cx5

• Allelic Composition: Irf8^tm1Hor/Irf8^tm1Hor; Irf4^tm1Mak/Irf4^tm1Mak
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

abnormal B cell differentiation ( J:84577 )

arrested B cell differentiation ( J:84577 )

• B cell development blocked in bone marrow at the pre-B cell stage

decreased dendritic cell number ( J:97716 )

• numbers of double negative dendritic cells reduced in spleen to half of control levels and very few found in thymus

decreased plasmacytoid dendritic cell number ( J:97716 )

• plasmacytoid dendritic cells in spleen reduced considerably

decreased lymphocyte cell number ( J:84577 )

absent B cells ( J:84577 )

• peripheral B cells lacking

decreased T cell number ( J:84577 )

• reduced numbers of both types of single positive T cells

abnormal pre-B cell morphology ( J:84577 )

• display cytoplasmic mu heavy chain and high levels of preBCR

• pre-B cells held up is S and G2 phase of cell cycle

increased pre-B cell number ( J:84577 )

• 5 fold increase in numbers

decreased IgM level ( J:84577 )

• soluble IgM lacking

hematopoietic system

abnormal B cell differentiation ( J:84577 )

arrested B cell differentiation ( J:84577 )

• B cell development blocked in bone marrow at the pre-B cell stage

decreased dendritic cell number ( J:97716 )

• numbers of double negative dendritic cells reduced in spleen to half of control levels and very few found in thymus

decreased plasmacytoid dendritic cell number ( J:97716 )

• plasmacytoid dendritic cells in spleen reduced considerably

decreased lymphocyte cell number ( J:84577 )

absent B cells ( J:84577 )

• peripheral B cells lacking

decreased T cell number ( J:84577 )

• reduced numbers of both types of single positive T cells

abnormal pre-B cell morphology ( J:84577 )

• display cytoplasmic mu heavy chain and high levels of preBCR

• pre-B cells held up is S and G2 phase of cell cycle

increased pre-B cell number ( J:84577 )

• 5 fold increase in numbers

decreased IgM level ( J:84577 )

• soluble IgM lacking

Genotype
MGI:5486202

cx6

• Allelic Composition: Id2^tm1Gtbz/Id2^tm1Gtbz; Irf8^tm1Hor/Irf8^tm1Hor
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

hematopoietic system

abnormal bone marrow cell morphology/development ( J:194760 )

• in reconstitution assays, bone marrow cells are not able to generate CD8alpha+ dendritic cells