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Blood, 15 January 2006, Vol. 107, No. 2, pp. 786-795.
Prepublished online as a Blood First Edition Paper on October 6, 2005; DOI 10.1182/blood-2005-05-1822.
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PHAGOCYTES
Developmental and functional significance of the CSF-1 proteoglycan chondroitin sulfate chain
Sayan Nandi,
Mohammed P. Akhter,
Mark F. Seifert,
Xu-Ming Dai, and
E. Richard Stanley
From the Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY; the Osteoporosis Research Center, Creighton University, Omaha, NE; and the Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN.
The primary macrophage growth factor, colony-stimulating factor-1 (CSF-1), is homodimeric and exists in 3 biologically active isoforms: a membrane-spanning, cell-surface glycoprotein (csCSF-1) and secreted glycoprotein (sgCSF-1) and proteoglycan (spCSF-1) isoforms. To investigate the in vivo role of the chondroitin sulfate glycosaminoglycan (GAG) chain of spCSF-1, we created mice that exclusively express, in a normal tissue-specific and developmental manner, either the secreted precursor of spCSF-1 or the corresponding precursor in which the GAG addition site was mutated. The reproductive, hematopoietic tooth eruption and tissue macrophage defects of CSF-1-deficient, osteopetrotic Csf1op/Csf1op mice were corrected by transgenic expression of the precursors of either sgCSF-1 or spCSF-1. Furthermore, in contrast to the transgene encoding csCSF-1, both failed to completely correct growth retardation, suggesting a role for csCSF-1 in the regulation of body weight. However, spCSF-1, in contrast to sgCSF-1, completely resolved the osteopetrotic phenotype. Furthermore, in transgenic lines expressing different concentrations of sgCSF-1 or spCSF-1, spCSF-1 more efficiently corrected Csf1op/Csf1op defects of tooth eruption, eyelid opening, macrophage morphology, and B-cell deficiency than sgCSF-1. These results indicate an important role of the CSF-1 chondroitin sulfate proteoglycan in in vivo signaling by secreted CSF-1. (Blood. 2006;107:786-795)
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