Phenotypes Associated with This Genotype

Genotype
MGI:2652762

• Allelic Composition: Csf3^tm1Ard/Csf3^tm1Ard
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

hematopoietic system

impaired myelopoiesis ( J:20400 )

• homozygotes show a 50% decrease in granulopoietic precursor cells in the bone marrow, with reduced levels of granulocyte, macrophage, and blast progenitor cells

• G-CSF administration reverses the granulopoietic defect: one day of G-CSF administration increases circulating neutrophil levels to normal, and after 4 days of G-CSF administration, mutant bone marrows are morphologically indistinguishable from wild-type marrows

decreased leukocyte cell number ( J:20400 )

• homozygotes are viable, fertile, and developmentally normal with no overt signs of disease or significant changes in hemoglobin or platelet levels

• however, homozygotes exhibit leukopenia as a result of significant selective neutropenia

• some homozygotes exhibit reduced circulating lymphocyte levels; however, these changes are inconsistent

decreased neutrophil cell number ( J:20400 )

• homozygotes exhibit a severe chronic neutropenia, with blood neutrophil levels reduced to ~30% of wild-type levels

• however, no significant changes in circulating eosinophil numbers are observed

decreased monocyte cell number ( J:20400 )

• homozygotes display significantly reduced monocyte levels relative to wild-type mice

abnormal neutrophil physiology ( J:20400 )

• homozygotes exhibit impaired neutrophil mobilization in response to a single dose of G-CSF, with only 21% of wild-type circulating neutrophil levels at 3 hrs post-treatment

immune system

impaired myelopoiesis ( J:20400 )

• homozygotes show a 50% decrease in granulopoietic precursor cells in the bone marrow, with reduced levels of granulocyte, macrophage, and blast progenitor cells

• G-CSF administration reverses the granulopoietic defect: one day of G-CSF administration increases circulating neutrophil levels to normal, and after 4 days of G-CSF administration, mutant bone marrows are morphologically indistinguishable from wild-type marrows

decreased leukocyte cell number ( J:20400 )

• homozygotes are viable, fertile, and developmentally normal with no overt signs of disease or significant changes in hemoglobin or platelet levels

• however, homozygotes exhibit leukopenia as a result of significant selective neutropenia

• some homozygotes exhibit reduced circulating lymphocyte levels; however, these changes are inconsistent

decreased neutrophil cell number ( J:20400 )

• homozygotes exhibit a severe chronic neutropenia, with blood neutrophil levels reduced to ~30% of wild-type levels

• however, no significant changes in circulating eosinophil numbers are observed

decreased monocyte cell number ( J:20400 )

• homozygotes display significantly reduced monocyte levels relative to wild-type mice

abnormal neutrophil physiology ( J:20400 )

• homozygotes exhibit impaired neutrophil mobilization in response to a single dose of G-CSF, with only 21% of wild-type circulating neutrophil levels at 3 hrs post-treatment

increased susceptibility to bacterial infection ( J:20400 )

• homozygotes display a significantly impaired ability to control infection with Listeria monocytogenes, as shown by a 50% mortality rate at day 5 post-inoculation as well as diminished neutrophil and delayed monocyte increases in blood and reduced infection-driven granulopoiesis