Ko Yaping, Kobbe Birgit, Nicolae Claudia, Miosge Nicolai, Paulsson Mats, Wagener Raimund, Aszódi Attila
Center for Biochemistry, Medical Faculty, University of Cologne, D-50931 Cologne, Germany.
Mol Cell Biol. 2004 Feb;24(4):1691-9. doi: 10.1128/MCB.24.4.1691-1699.2004.
Matrilin-3 belongs to the matrilin family of extracellular matrix (ECM) proteins and is primarily expressed in cartilage. Mutations in the gene encoding human matrilin-3 (MATN-3) lead to autosomal dominant skeletal disorders, such as multiple epiphyseal dysplasia (MED), which is characterized by short stature and early-onset osteoarthritis, and bilateral hereditary microepiphyseal dysplasia, a variant form of MED characterized by pain in the hip and knee joints. To assess the function of matrilin-3 during skeletal development, we have generated Matn-3 null mice. Homozygous mutant mice appear normal, are fertile, and show no obvious skeletal malformations. Histological and ultrastructural analyses reveal endochondral bone formation indistinguishable from that of wild-type animals. Northern blot, immunohistochemical, and biochemical analyses indicated no compensatory upregulation of any other member of the matrilin family. Altogether, our findings suggest functional redundancy among matrilins and demonstrate that the phenotypes of MED disorders are not caused by the absence of matrilin-3 in cartilage ECM.
基质金属蛋白酶-3属于细胞外基质（ECM）蛋白的基质金属蛋白酶家族，主要在软骨中表达。编码人类基质金属蛋白酶-3（MATN-3）的基因突变会导致常染色体显性遗传性骨骼疾病，如多发性骨骺发育不良（MED），其特征为身材矮小和早发性骨关节炎，以及双侧遗传性微骨骺发育不良，这是MED的一种变体形式，其特征为髋关节和膝关节疼痛。为了评估基质金属蛋白酶-3在骨骼发育过程中的功能，我们培育了基质金属蛋白酶-3基因敲除小鼠。纯合突变小鼠外观正常，可育，且未表现出明显的骨骼畸形。组织学和超微结构分析显示，软骨内成骨与野生型动物无异。Northern印迹、免疫组织化学和生化分析表明，基质金属蛋白酶家族的任何其他成员均未出现代偿性上调。总之，我们的研究结果表明基质金属蛋白酶之间存在功能冗余，并证明MED疾病的表型并非由软骨ECM中缺乏基质金属蛋白酶-3所致。
