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  • Title: Perturbed granulopoiesis in mice with a targeted mutation in the granulocyte colony-stimulating factor receptor gene associated with severe chronic neutropenia.
    Author: Hermans MH, Ward AC, Antonissen C, Karis A, Löwenberg B, Touw IP.
    Journal: Blood; 1998 Jul 01; 92(1):32-9. PubMed ID: 9639496.
    Abstract:
    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-triangle Delta715) by homologous and Cre-mediated recombination in embryonic stem cells. Both wt/triangle Delta715 and triangle Delta715/triangle Delta715 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 triangle Delta715 mutation can contribute both to neutropenia and to neutrophilia.
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