Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1-deficient Csf1op/Csf1op mice by transgenic expression of cell surface CSF-1.
The primary macrophage growth factor, colony-stimulating factor 1 (CSF-1), is expressed as a secreted glycoprotein or proteoglycan found in the circulation or as a biologically active cell surface glycoprotein (csCSF-1). To investigate the in vivo roles of csCSF-1, we created mice that exclusively express csCSF-1, in a normal tissue-specific and developmental manner, by transgenic expression of csCSF-1 in the CSF-1-deficient osteopetrotic (Csf1(op)/Csf1(op)) background. The gross defects of Csf1(op)/Csf1(op) mice, including growth retardation, failure of tooth eruption, and abnormal male and female reproductive functions were corrected. Macrophage densities in perinatal liver, bladder, sublinguinal salivary gland, kidney cortex, dermis, and synovial membrane were completely restored, whereas only partial or no restoration was achieved in adult liver, adrenal gland, kidney medulla, spleen, peritoneal cavity, and intestine. Residual osteopetrosis, significantly delayed trabecular bone resorption in the subepiphyseal region of the long bone, and incomplete correction of the hematologic abnormalities in the peripheral blood, bone marrow, and spleens of CSF-1-deficient mice were also found in mice exclusively expressing csCSF-1. These data suggest that although csCSF-1 alone is able to normalize several aspects of development in Csf1(op)/Csf1(op) mice, it cannot fully restore in vivo CSF-1 function, which requires the presence of the secreted glycoprotein and/or proteoglycan forms.
Dai
Xu-Ming
XM
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Zong
Xiao-Hua
XH
Sylvestre
Vonetta
V
Stanley
E Richard
ER
D000818:Animals; D001862:Bone Resorption / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006410:Hematopoiesis / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009805:Odontogenesis / Q000235:genetics; D010022:Osteopetrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012098:Reproduction / Q000235:genetics
D016173:Macrophage Colony-Stimulating Factor