Correction by CSF-1 of defects in the osteopetrotic op/op mouse suggests local, developmental, and humoral requirements for this growth factor.
Mice that are mutant at the op locus have a severe deficiency of mononuclear phagocytes due to an inactivating mutation in the CSF-1 (macrophage colony-stimulating factor, M-CSF) gene. op/op mice are toothless, possessing skeletal abnormalities, a low body weight, and compromised fertility; they are osteopetrotic due to a deficiency of osteoclasts. The congenital osteopetrosis, toothless phenotype, osteoclast deficit, and the defects in splenic and femoral macrophages were corrected by routes of administration of human recombinant CSF-1 that maintained normal circulating CSF-1 concentrations. Early restoration of circulating CSF-1 was required for rescue of the toothless phenotype, but only partially restored body weight. In contrast, the deficiencies of pleural and peritoneal cavity macrophages and the reduced female fertility were not corrected by restoration of circulating CSF-1. These results suggest that although circulating CSF-1 is required for osteoclast and macrophage production, local synthesis and action of the growth factor are important for certain target cell populations.
Wiktor-Jedrzejczak
W
W
Department of Immunology, Military School of Medicine, Warsaw, Poland.
Urbanowska
E
E
Aukerman
S L
SL
Pollard
J W
JW
Stanley
E R
ER
Ralph
P
P
Ansari
A A
AA
Sell
K W
KW
Szperl
M
M
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D005269:Femur / Q000473:pathology; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D010010:Osteoclasts / Q000473:pathology; D010022:Osteopetrosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010529:Peritoneal Cavity / Q000473:pathology; D010994:Pleura / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000473:pathology; D014078:Tooth Eruption
D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor