Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice

Proceedings of the National Academy of Sciences of the United States of America - Tập 95 Số 16 - Trang 9448-9453 - 1998
Qing Ma1, Dan Jones1, Paul R. Borghesani1, Rosalind A. Segal1, Takashi Nagasawa1, Tadamitsu Kishimoto1, Roderick T. Bronson1, Timothy A. Springer1
1The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; Department of Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka 590-02, Japan; Department of Medicine III, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565, Japan; and Department of Pathology, Tufts University School...

Tóm tắt

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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 95 Số 16

9448-9453

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