Enamelysin (matrix metalloproteinase 20)-deficient mice display an amelogenesis imperfecta phenotype
Enamelysin (matrix metalloproteinase 20)-deficient mice display an amelogenesis imperfecta phenotype
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DOI：
10.1074/jbc.m209100200
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发表时间：
2002-12-20
影响因子：
4.8
通讯作者：
Bartlett, JD
中科院分区：
文献类型：
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作者：
Caterina, JJ;Skobe, Z;Bartlett, JD
釉质溶素是一种牙齿特异的基质金属蛋白酶，在釉质发育的早期到中期都有表达。釉质基质蛋白成釉蛋白、成釉蛋白和成釉蛋白在相同的发育时期也有表达，提示釉质溶素可能在它们的水解过程中起作用。为了支持这一解释，重组釉原蛋白先前被证明在几乎所有已知的体内发生的精确位置上切割重组釉原蛋白。因此，釉质溶素可能是一种重要的釉原蛋白加工酶。为了研究釉质溶素在牙齿发育过程中的生物学作用，我们通过基因打靶的方法产生了一只釉质溶素缺陷小鼠。虽然突变杂合子的小鼠没有明显的表型，但釉解素缺失的小鼠有严重而深刻的牙齿表型。具体地说，空小鼠不能正确地处理釉原蛋白，具有改变的釉质基质和杆状图案，具有从牙本质剥离的发育不全的釉质，并且随着发育的进展，釉质器官的形态不断恶化。我们的发现表明，釉质溶血素的活性对釉质的正常发育是必不可少的。
Enamelysin is a tooth-specific matrix metalloproteinase that is expressed during the early through middle stages of enamel development. The enamel matrix proteins amelogenin, ameloblastin, and enamelin are also expressed during this same approximate developmental time period, suggesting that enamelysin may play a role in their hydrolysis. In support of this interpretation, recombinant enamelysin was previously demonstrated to cleave recombinant amelogenin at virtually all of the precise sites known to occur in vivo. Thus, enamelysin is likely an important amelogenin-processing enzyme. To characterize the in vivo biological role of enamelysin during tooth development, we generated an enamelysin-deficient mouse by gene targeting. Although mice heterozygous for the mutation have no apparent phenotype, the enamelysin null mouse has a severe and profound tooth phenotype. Specifically, the null mouse does not process amelogenin properly, possesses an altered enamel matrix and rod pattern, has hypoplastic enamel that delaminates from the dentin, and has a deteriorating enamel organ morphology as development progresses. Our findings demonstrate that enamelysin activity is essential for proper enamel development.