Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice
Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice
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DOI：
10.1038/sj.onc.1207688
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发表时间：
2004-06-24
期刊：
影响因子：
8
通讯作者：
Noda, M
中科院分区：
文献类型：
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作者：
Oh, J;Takahashi, R;Noda, M
基质金属蛋白酶 (MMP) 家族（类似于哺乳动物中的 25 个成员）参与与胚胎发育、癌症形成和进展以及各种其他生理和病理事件相关的细胞外基质重塑。然而，迄今为止所描述的小鼠个体基质金属蛋白酶基因的失活突变至少在出生后的最初几周内是非致命的，这表明 MMP 家族成员之间存在功能冗余。在此，我们报道缺乏两种 MMP（MMP-2（非膜型）和 MT1-MMP（膜型））的小鼠在出生后立即死亡，并出现呼吸衰竭、血管异常和不成熟的肌纤维（让人想起中枢核心疾病）。在缺乏MMP-2和MT1-MMP的情况下，体外成肌细胞融合也显着延迟。这些发现表明，两种具有不同分子性质的 MMP 在小鼠体内存在功能重叠。
The matrix metalloproteinase (MMP) family (similar to25 members in mammals) has been implicated in extracellular matrix remodeling associated with embryonic development, cancer formation and progression, and various other physiological and pathological events. Inactivating mutations in individual matrix metalloproteinase genes in mice described so far, however, are nonlethal at least up to the first few weeks after birth, suggesting functional redundancy among MMP family members. Here, we report that mice lacking two MMPs, MMP-2 (nonmembrane type) and MT1-MMP ( membrane type), die immediately after birth with respiratory failure, abnormal blood vessels, and immature muscle fibers reminiscent of central core disease. In the absence of MMP-2 and MT1-MMP, myoblast fusion in vitro is also significantly retarded. These findings suggest functional overlap in mice between the two MMPs with distinct molecular natures.