Functional analysis of the alpha10beta1 integrin

Abstract: The aim of this thesis was to study the function of the integrin a10b1. Integrins mediate signals between cells and their environment and regulate several cellular processes such as cell migration, proliferation and differentiation. The a10b1 integrin is expressed mainly by chondrocytes, the only cell type present in cartilage, and facilitates binding of the chondrocytes to the extracellular matrix molecule collagen. However, the function of the a10b1 integrin in cartilage is not known. In this thesis we describe the structure of the mouse a10b1 integrin gene and report the finding of two alternatively spliced extracellular forms of the a10b1 integrin. We also demonstrate the chromosomal localization of the human and mouse a10 integrin genes. To analyze the role of this collagen-binding integrin during development and in adult mice we generated a mouse deficient in the a10b1 integrin, by gene targeting deletion. We found that a10b1–null mice suffered from a mild chondrodysplasia, and that they had shorter limbs than normal mice. The mutant mice showed structural defects in the growth plate and decreased chondrocyte proliferation. Further studies have revealed that the a10b1 integrin appears to be the only collagen-binding integrin expressed in the growth plate of 8-week old mice. Together, these data show that the a10b1 integrin plays an important role in the regulation of chondrocyte function and bone development.