Gill Sean E, Kassim Sean Y, Birkland Timothy P, Parks William C
Center for Lung Biology, University of Washington School of Medicine, Seattle, WA, USA.
Methods Mol Biol. 2010;622:31-52. doi: 10.1007/978-1-60327-299-5_2.
As their name implies, matrix metalloproteinases (MMPs) are thought to be responsible for the turnover of connective tissue proteins, a function that is indeed performed by some family members. However, matrix degradation is possibly not the predominant function of these enzymes. Several studies have demonstrated that MMPs also act on a variety of non-matrix extracellular proteins, such as cytokines, chemokines, receptors, junctional proteins, and antimicrobial peptides, to mediate a wide range of biological processes, such as repair, immunity, and angiogenesis. Our understanding of the many, diverse and, at times, unexpected functions of MMPs largely arose from the use of gene-targeted mice. In this chapter, we discuss the phenotypes of some MMP-deficient and TIMP-null mice and strategies and pitfalls in targeted mutagenesis.
顾名思义，基质金属蛋白酶（MMPs）被认为负责结缔组织蛋白的更新，这一功能确实由一些家族成员执行。然而，基质降解可能并非这些酶的主要功能。多项研究表明，MMPs还作用于多种非基质细胞外蛋白，如细胞因子、趋化因子、受体、连接蛋白和抗菌肽，以介导广泛的生物学过程，如修复、免疫和血管生成。我们对MMPs众多、多样且有时意想不到的功能的理解很大程度上源于对基因靶向小鼠的研究。在本章中，我们将讨论一些MMP缺陷和TIMP基因敲除小鼠的表型以及靶向诱变的策略和陷阱。
