title: Perturbed granulopoiesis in mice with a targeted mutation in the granulocyte colony-stimulating factor receptor gene associated with severe chronic neutropenia.
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.
authors.affiliation: Institute of Hematology, Daniel den Hoed Cancer Center and Erasmus University Rotterdam, Rotterdam, The Netherlands.
authors.forename: M H
authors.initials: MH
authors.lastname: Hermans
authors.forename: A C
authors.initials: AC
authors.lastname: Ward
authors.forename: C
authors.initials: C
authors.lastname: Antonissen
authors.forename: A
authors.initials: A
authors.lastname: Karis
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
authors.forename: I P
authors.initials: IP
authors.lastname: Touw
mesh_terms: D000818:Animals; D002908:Chronic Disease; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000502:physiology; D006098:Granulocytes / Q000166:cytology / Q000502:physiology*; D006410:Hematopoiesis / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009503:Neutropenia / Q000235:genetics* / Q000517:prevention & control; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D011995:Recombination, Genetic
chemical_list: D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor