Osteopetrosis in mice lacking NF-kappa B1 and NF-kappa B2
Osteopetrosis in mice lacking NF-kappa B1 and NF-kappa B2
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DOI：
10.1038/nm1197-1285
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发表时间：
1997-11-01
期刊：
影响因子：
82.9
通讯作者：
Bravo, R
中科院分区：
文献类型：
--
作者：
Iotsova, V;Caamano, J;Bravo, R
nfkb 1和nfkb 2基因编码调节免疫和炎症反应的密切相关的产物。它们在发育和分化过程中的作用仍不清楚。nfkb 1基因敲除小鼠（p50（-/-））的产生导致了免疫反应的改变，但对发育没有影响（4）。类似地，nfkb 2敲除小鼠（p52（-/-））未显示发育缺陷（J.C.等，已提交手稿）。我们已经研究了潜在的体内代偿功能，这些基因产生的双敲除小鼠。令人惊讶的结果是，由于破骨细胞分化的缺陷，动物发生了骨硬化症，这表明NF-κ B1和NF-κ B2蛋白在该细胞谱系的发育中具有冗余功能。骨髓移植挽救了骨硬化表型，表明造血成分受损。这些结果定义了一种新的小鼠骨硬化突变体，并暗示NF-κ B蛋白在骨发育中的作用，为骨疾病的治疗提供了新的方向。
The nfkb1 and nfkb2 genes encode closely related products regulating immune and inflammatory responses. Their role during development and differentiation remains unclear. The generation of nfkb1 null mice (p50(-/-)) resulted in altered immune responses, but had no effect on development(4). Similarly, nfkb2 knockout mice (p52(-/-)) did not show developmental defects (J.C. et ol., manuscript submitted). We have investigated the potential for in vivo compensatory functions of these genes by generating double-knockout mice. The surprising result was that the animals developed osteopetrosis because of a defect in osteoclast differentiation, suggesting redundant functions of NF-kappa B1 and NF-kappa B2 proteins in the development of this cell lineage. The osteopetrotic phenotype was rescued by bone marrow transplantation, indicating that the hematopoietic component was impaired. These results define a new mouse osteopetrotic mutant and implicate NF-kappa B proteins in bone development, raising new directions in the treatment of bone disorders.