Matrilin-3 Is Dispensable for Mouse Skeletal Growth and Development

Abstract

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.

We thank Catarina Cramnert and Zsuzsanna Farkas for technical assistance, Kathrin Rodgers for reading the manuscript, and Reinhard Fässler (MPI, Department of Molecular Medicine) for supporting the project.

This study was supported by grants from the Deutsche Forschungsgemeinschaft (AS 150/1-1, WA 1338/2-1, WA 1338/2-2, and WA 1338/2-3), the Max-Planck Society, the Swedish Medical Research Council, the Anna-Greta Crafoords Foundation, the Greta and Johan Kocks Foundation, and the Köln Fortune program of the Medical Faculty of the University of Cologne. Y.K. is a student in the International Graduate School in Genetics and Functional Genomics at the University of Cologne, funded by the State of Northrhine-Westphalia.