Matrix Biology 23 (2004) 195–204 0945-053X/04/$30.00  2004 Elsevier B.V./International Society of Matrix Biology. All rights reserved. doi:10.1016/j.matbio.2004.05.003 Mice lacking the extracellular matrix adaptor protein matrilin-2 develop without obvious abnormalities Lajos Mates , Claudia Nicolae , Matthias Morgelin , Ferenc Deak , Ibolya Kiss , Attila Aszodi * a b c a a b, ´´ ¨ ´ ´ Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, H-6701 Szeged, Hungary a Department for Molecular Medicine, Max Planck Institute for Biochemistry, Am Klopferspitz 18A, D-82152 Martinsried, Germany b Department of Cell and Molecular Biology, Section of Molecular Pathogenesis, BMCyB14, University of Lund, S-22184 Lund, Sweden c Received 15 January 2004; received in revised form 28 April 2004; accepted 5 May 2004 Abstract Matrilins are putative adaptor proteins of the extracellular matrix (ECM) which can form both collagen-dependent and collagen- independent filamentous networks. While all known matrilins (matrilin-1, -2, -3, and -4) are expressed in cartilage, only matrilin- 2 and matrilin-4 are abundant in non-skeletal tissues. To clarify the biological role of matrilin-2, we have developed a matrilin-2-deficient mouse strain. Matrilin-2 null mice show no gross abnormalities during embryonic or adult development, are fertile, and have a normal lifespan. Histological and ultrastructural analyses indicate apparently normal structure of all organs and tissues where matrilin-2 is expressed. Although matrilin-2 co-localizes with matrilin-4 in many tissues, Northern hybridization, semiquantitative RT-PCR, immunohistochemistry and biochemical analysis reveal no significant alteration in the steady-state level of matrilin-4 expression in homozygous mutant mice. Immunostaining of wild-type and mutant skin samples indicate no detectable differences in the expression and deposition of matrilin-2 binding partners including collagen I, laminin-nidogen complexes, fibrillin-2 and fibronectin. In addition, electron microscopy reveals an intact basement membrane at the epidermal–dermal junction and normal organization of the dermal collagen fibrils in mutant skin. These data suggest that either matrilin-2 and matrilin-2- mediated matrix–matrix interactions are dispensable for proper ECM assembly and function, or that they are efficiently compensated by other matrix components including wild-type levels of matrilin-4.  2004 Elsevier B.V./International Society of Matrix Biology. All rights reserved. Keywords: Extracellular matrix; Matrilin; Cartilage; Skin 1. Introduction Extracellular matrices (ECMs) are highly organized structures that perform diverse roles during development, tumorigenesis, and tissue repair. The cell modifying actions of ECM components are partially mediated by intracellular signals induced by ECM ligands binding cellular receptors. Further interactions between different matrix proteins are essential for proper ECM assembly and play a crucial role in maintaining the structural integrity and physical properties of connective tissues. The multifunctional nature of ECM components is high- lighted by the relatively limited set of modules found to comprise most of these proteins. The matrilins are a family of ECM proteins, which share similar modular structure. The family consists of *Corresponding author. Tel.: q49-89-8578-2849; fax: q49-89- 8578-2422. E-mail address: aszodi@biochem.mpg.de (A. Aszodi). ´ four members (matrilin-1, -2, -3, and -4), each carrying one or two von Willebrand factor A (vWFA)-like mod- ules, a various number of epidermal growth factor (EGF)-like motifs, and a coiled-coil (CC) oligomeriza- tion domain (reviewed in Deak et al., 1999). Matrilin-1 ´ and -3 are expressed primarily in cartilage, while matri- lin-2 and -4 have a broader tissue distribution. Matrilin- 2 is the largest member of the family. Analysis of the mouse and human matrilin-2 cDNA sequences revealed that the precursor protein consists of a putative signal peptide, two vWFA-like domains separated by ten EGF- like motifs, a unique segment not identified in other matrilins, and a CC domain (Deak et al., 1997; Mura- ´ toglu et al., 2000). In tissue extracts and cell culture medium, matrilin-2 exists as mono-, di-, tri-, and tetra- mers, as demonstrated by SDS-PAGE and electron microscopy (Piecha et al., 1999). In addition to forming homotypic oligomers, biochemical and biophysical