Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse.
Osteopetrotic (op/op) mutant mice suffer from congenital osteopetrosis due to a severe deficiency of osteoclasts. Furthermore, the total number of mononuclear phagocytes is extremely low in affected mice. Serum, 11 tissues, and different cell and organ conditioned media from op/op mice were shown to be devoid of biologically active colony-stimulating factor 1 (CSF-1), whereas all of these preparations from littermate control +/+ and +/op mice contained the growth factor. The deficiency was specific for CSF-1 in that serum or conditioned media from op/op mice possessed elevated levels of at least three other macrophage growth factors. Partial correction of the op/op defect was observed following intraperitoneal implantation of diffusion chambers containing L929 cells, which in culture produce CSF-1 as their sole macrophage growth factor. No rearrangement of the CSF-1 gene in op/op mice was detected by Southern analysis. However, in contrast to control lung fibroblasts, which contained 4.6- and 2.3-kilobase CSF-1 mRNAs, only the 4.6-kilobase species was detected in op/op cells. An alteration in the CSF-1 gene is strongly implicated as the primary defect in op/op mice because they do not contain detectable CSF-1, their defect is correctable by administration of CSF-1, the op locus and the CSF-1 gene map within the same region of mouse chromosome 3, their CSF-1 mRNA biosynthesis is altered, and the op/op phenotype is consistent with the phenotype expected in a CSF-1 deficient mouse.
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322.
W
W
Wiktor-Jedrzejczak
A
A
Bartocci
A W
AW
Ferrante
A
A
Ahmed-Ansari
K W
KW
Sell
J W
JW
Pollard
E R
ER
Stanley
D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000235:genetics / Q000378:metabolism*; D003433:Crosses, Genetic; D003470:Culture Media; D004247:DNA / Q000032:analysis; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010022:Osteopetrosis / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012016:Reference Values
D003115:Colony-Stimulating Factors; D003470:Culture Media; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA