Normal Skeletal Development of Mice Lacking Matrilin 1: Redundant Function of Matrilins in Cartilage?

Abstract

Matrilin 1, or cartilage matrix protein, is a member of a novel family of extracellular matrix proteins. To date, four members of the family have been identified, but their biological role is unknown. Matrilin 1 and matrilin 3 are expressed in cartilage, while matrilin 2 and matrilin 4 are present in many tissues. Here we describe the generation and analysis of mice carrying a null mutation in the Crtm gene encoding matrilin 1. Anatomical and histological studies demonstrated normal development of homozygous mutant mice. Northern blot and biochemical analyses show no compensatory up-regulation of matrilin 2 or 3 in the cartilage of knockout mice. Although matrilin 1 interacts with the collagen II and aggrecan networks of cartilage, suggesting that it may play a role in cartilage tissue organization, studies of collagen extractability indicated that collagen fibril maturation and covalent cross-linking were unaffected by the absence of matrilin 1. Ultrastructural analysis did not reveal any abnormalities of matrix organization. These data suggest that matrilin 1 is not critically required for cartilage structure and function and that matrilin 1 and matrilin 3 may have functionally redundant roles.

ACKNOWLEDGMENTS

We thank Ray Boot-Handford and Mats Paulsson for discussion and critical reading of the manuscript. Sue Golub is thanked for technical assistance.

This study was supported by the Swedish Medical Research Council (no. K98-12X-12531-01A), the Volkswagen-Stiftung (no. I/70621), OTKA (no. T023838), and the University of Melbourne Collaborative Research Grants Scheme.