Perturbed granulopoiesis in mice with a targeted mutation in the granulocyte colony-stimulating factor receptor gene associated with severe chronic neutropenia

被引:90
作者
Hermans, MHA
Ward, AC
Antonissen, C
Karis, A
Löwenberg, B
Touw, IP
机构
[1] Erasmus Univ, Inst Hematol, NL-3000 DR Rotterdam, Netherlands
[2] Dr Daniel Den Hoed Canc Ctr, Inst Hematol, NL-3008 AE Rotterdam, Netherlands
[3] Erasmus Univ, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands
关键词
D O I
10.1182/blood.V92.1.32.413k42_32_39
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-Delta 715) by homologous and Cre-mediated recombination in embryonic stem cells. Both wt/Delta 715 and Delta 715/Delta 715 mice have significantly reduced numbers of blood neutrophils compared with their wt/wtlittermates. 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 Delta 715 mutation can contribute both to neutropenia and to neutrophilia. (C) 1998 by The American Society of Hematology.
引用
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页码:32 / 39
页数:8
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