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PMID: 9689100 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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 ·Vol. 95 ·No. 16 ·1998-08-04 ·Pages 9448-53

Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA

Abstract

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.

MeSH Terms
Animals B-Lymphocytes/cytology Base Sequence Bone Marrow Cells/cytology Cell Movement Cells, Cultured Cerebellum/cytology Chemokine CXCL12 Chemokines, CXC/genetics DNA Primers Hematopoiesis Mice Neurons/cytology Phenotype Receptors, CXCR4/genetics
Chemicals
Chemokine CXCL12 Chemokines, CXC Cxcl12 protein, mouse DNA Primers Receptors, CXCR4
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Ma Q
The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Jones D
Borghesani P R
Segal R A
Nagasawa T
Kishimoto T
Bronson R T
Springer T A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.16.9448
Published
1998-08-04
Pages
9448-53
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21358
Subset
IM
Grants
NHLBI NIH HHS · P01 HL048675 · United States
NHLBI NIH HHS · HL-48675 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.16.9448 PMC Full Text View journal details
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