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Perturbed Granulopoiesis in Mice With a Targeted Mutation in the Granulocyte Colony-Stimulating Factor Receptor Gene Associated With Severe Chronic Neutropenia

1998; Elsevier BV; Volume: 92; Issue: 1 Linguagem: Inglês

10.1182/blood.v92.1.32.413k42_32_39

1528-0020

Mirjam H. A. Hermans, Alister C. Ward, Claudia Antonissen, Alar Karis, Bob Löwenberg, Ivo P. Touw,

Immunodeficiency and Autoimmune Disorders

Mutations in the granulocyte colony-stimulating factor (G-CSF) receptor gene are found in a number of patients with severe chronic neutropenia predisposed to acute myeloid leukemia. These mutations result in the absence of the C-terminal domain of the G-CSF-R, a region which has been implicated in differentiation signaling. We generated mice with an equivalent mutation (gcsfr-▵715) by homologous and Cre-mediated recombination in embryonic stem cells. Both wt/▵715 and▵715/▵715 mice have significantly reduced numbers of blood neutrophils compared with their wt/wt littermates. However, under continuous G-CSF administration mutant mice develop peripheral neutrophil counts that significantly exceed those of wild-type littermates. These findings indicate that depending on G-CSF levels in mice, the ▵715 mutation can contribute both to neutropenia and to neutrophilia.