Ma Q, Jones D, Borghesani P R, Segal R A, Nagasawa T, Kishimoto T, Bronson R T, Springer T A
The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9448-53. doi: 10.1073/pnas.95.16.9448.
The chemokine stromal cell-derived factor 1, SDF-1, is an important regulator 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.
趋化因子基质细胞衍生因子1（SDF-1）是白细胞和造血前体细胞迁移以及前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进入细胞的共受体。我们发现CXCR4基因缺陷的小鼠在围产期死亡，并在造血系统和神经系统中表现出严重缺陷。CXCR4基因缺陷的小鼠B淋巴细胞生成严重减少，胎肝中的髓细胞生成减少，骨髓中几乎没有髓细胞生成。然而，T淋巴细胞生成未受影响。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，小脑原基内有大量异常迁移的颗粒细胞形成的嗜色细胞团。在缺乏SDF-1的小鼠中也观察到相同的缺陷，这表明CXCR4和SDF-1之间存在一对一的关系。这种受体-配体的选择性在趋化因子及其受体中是不常见的，在非造血细胞迁移中的功能也是如此。
