Perturbed granulopoiesis in mice with a targeted mutation in the granulocyte colony-stimulating factor receptor gene associated with severe chronic neutropenia
Version 2 2024-06-03, 21:45Version 2 2024-06-03, 21:45
Version 1 2017-05-16, 15:56Version 1 2017-05-16, 15:56
journal contribution
posted on 2024-06-03, 21:45authored byMH Hermans, Alister WardAlister Ward, C Antonissen, A Karis, B Löwenberg, IP Touw
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.