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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.
Previous Article | Next Article 
Submitted May 5, 2005
Accepted August 25, 2005
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*
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA
Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA
* Corresponding author; email: rstanley{at}aecom.yu.edu.
The primary macrophage growth factor, colony stimulating factor-1 (CSF-1), is homodimeric and exists in three 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 sg or sp CSF-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.

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