PDF(Pubmed)
Abstract：
The fibrillinopathies represent a group of diseases in which the 10-12 nm extracellular microfibrils are disrupted by genetic variants in one of the genes encoding fibrillin molecules, large glycoproteins of the extracellular matrix. The best-known fibrillinopathy is Marfan syndrome, an autosomal dominant condition affecting the cardiovascular, ocular, skeletal, and other systems, with a prevalence of around 1 in 3,000 across all ethnic groups. It is caused by variants of the FBN1 gene, encoding fibrillin-1, which interacts with elastin to provide strength and elasticity to connective tissues. A number of mouse models have been created in an attempt to replicate the human phenotype, although all have limitations. There are also natural bovine models and engineered models in pig and rabbit. Variants in FBN2 encoding fibrillin-2 cause congenital contractural arachnodactyly and mouse models for this condition have also been produced. In most animals, including birds, reptiles, and amphibians, there is a third fibrillin, fibrillin-3 (FBN3 gene) for which the creation of models has been difficult as the gene is degenerate and nonfunctional in mice and rats. Other eukaryotes such as the nematode C. elegans and zebrafish D. rerio have a gene with some homology to fibrillins and models have been used to discover more about the function of this family of proteins. This review looks at the phenotype, inheritance, and relevance of the various animal models for the different fibrillinopathies.
摘要：
原纤病代表一组疾病，其中10-12nm的细胞外微原纤维被编码原纤蛋白分子的基因之一的遗传变异破坏，细胞外基质的大糖蛋白。最著名的纤丝蛋白病是马凡氏综合征,影响心血管的常染色体显性疾病，眼,骨骼，和其他系统，在所有种族中，患病率约为3,000人中的1人。它是由FBN1基因的变异引起的，编码原纤维蛋白-1，它与弹性蛋白相互作用，为结缔组织提供强度和弹性。为了复制人类表型，已经创建了许多小鼠模型，虽然都有局限性。在猪和兔中也有天然牛模型和工程模型。FBN2编码纤丝蛋白-2的变体会导致先天性挛缩蛛网膜畸形，并且还产生了这种情况的小鼠模型。在大多数动物中，包括鸟类,爬行动物,和两栖动物,还有第三种纤丝蛋白，原纤维蛋白-3（FBN3基因），由于该基因在小鼠和大鼠中退化且无功能，因此难以创建模型。其他真核生物，例如线虫C.elegans和斑马鱼D.rerio具有与原纤维蛋白具有某些同源性的基因，并且已使用模型来发现有关该蛋白质家族功能的更多信息。这篇综述着眼于表型，继承,和各种动物模型对不同的原纤病的相关性。
