TOTAL ABSENCE OF COLONY-STIMULATING FACTOR 1 IN THE MACROPHAGE-DEFICIENT OSTEOPETROTIC (OP OP) MOUSE
TOTAL ABSENCE OF COLONY-STIMULATING FACTOR 1 IN THE MACROPHAGE-DEFICIENT OSTEOPETROTIC (OP OP) MOUSE
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DOI：
10.1073/pnas.87.12.4828
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发表时间：
1990-06-01
影响因子：
11.1
通讯作者：
STANLEY, ER
中科院分区：
文献类型：
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作者：
WIKTORJEDRZEJCZAK, W;BARTOCCI, A;STANLEY, ER
石骨症（op/op）突变小鼠由于破骨细胞的严重缺乏而患有先天性石骨症。此外，在受影响的小鼠中单核吞噬细胞的总数极低。来自op/op小鼠的血清、11种组织以及不同细胞和器官条件培养基显示不含生物活性集落刺激因子1（CSF-1），而来自同窝对照+/+和+/op小鼠的所有这些制剂均含有生长因子。缺乏症是CSF-1特异性的，因为来自op/op小鼠的血清或条件培养基具有升高水平的至少三种其他巨噬细胞生长因子。腹膜内植入含有L929细胞的扩散室后，观察到op/op缺陷的部分纠正，L929细胞在培养中产生CSF-1作为其唯一的巨噬细胞生长因子。Southern分析未检测到OP/OP小鼠CSF-1基因重排。然而，与含有4.6千碱基和2.3千碱基CSF-1 mRNA的对照肺成纤维细胞相反，在op/op细胞中仅检测到4.6千碱基物质。CSF-1基因的改变强烈暗示为op/op小鼠中的主要缺陷，因为它们不含可检测的CSF-1，它们的缺陷可通过施用CSF-1、op基因座和小鼠染色体3的相同区域内的CSF-1基因图谱来纠正，它们的CSF-1 mRNA生物合成被改变，并且op/op表型与CSF-1缺陷小鼠中预期的表型一致。
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 chromsome 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.