Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice
Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice
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DOI：
10.1073/pnas.95.16.9448
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Springer, TA
中科院分区：
文献类型：
--
作者：
Ma, Q;Jones, D;Springer, TA
趋化因子SDF-1是白细胞和造血祖细胞迁移及前B细胞增殖的重要调节因子。SDF-1的受体CXCR4也是T嗜性HIV-1进入的辅助受体。我们发现，缺乏CXCR4的小鼠会在围产期死亡，并在造血和神经系统方面表现出严重的缺陷。CXCR4基因缺陷的小鼠已经严重减少了B淋巴细胞的生成，减少了胎肝的骨髓生成，并且骨髓中几乎没有骨髓生成。然而，T淋巴细胞的生成不受影响。此外，小脑发育异常，外部颗粒细胞层不规则，浦肯野细胞异位分布，小脑原基内有大量异常迁移的颗粒细胞嗜铬细胞团，缺乏SDF-1的小鼠出现相同的缺陷，提示CXCR4和SDF-1之间存在单性关系。这种受体-配体的选择性在趋化因子及其受体中是不寻常的，在非造血细胞的迁移中也是如此。
The chemokime stromal cell-depived factor 1, SDF-1, is an important regulates of leukocyte and hematopoietic precursor migration and pre-B cell proliferation. The receptor for SDF-1, CXCR4, also functions as a coreceptor For T-tropic HIV-1 entry. We find that mice deficient for CXCR4 die perinatally and display profound defects in the hematopoietic and nervous systems. CXCR4-deficient mice have severely reduced B-lymphopoiesis, reduced myelopoiesis in fetal liver, and a virtual absence of myelopoiesis in bone marrow. However, T-lymphopoiesis is unaffected. Furthermore, the cerebellum develops abnormally with an irregular external granule cell layer, ectopically located Purkinje cells, and numerous chromophilic cell clumps of abnormally migrated granule cells within the cerebellar anlage, Identical defects are observed in mice lacking SDF-1, suggesting a monogamous relationship between CXCR4 and SDF-1. This receptor-ligand selectivity is unusual among chemokines and their receptors, as is the function in migration of nonhematopoietic cells.