EXPRESSION AND FUNCTIONAL-ANALYSIS OF MOUSE EXT1, A HOMOLOG OF THE HUMAN MULTIPLE EXOSTOSES TYPE-1 GENE

Hereditary multiple exostoses (EXT) is a genetically heterogeneous, au tosomal dominant skeletal disorder. The gene for EXT1 maps to human ch romosome 8q24.1 and encodes an evolutionary conserved protein that is a member of a multigene family. The mouse homolog of human EXT1 protei n is 99% similar to its human counterpart. Here, we present the expres sion profiles of the mouse EXT1 gene. EXT1 mRNA is initially expressed at 6.5 days post-coitum (d.p.c.), which coincides with gastrulation o f the mouse embryo. Whole mount in situ hybridization with 10.5 to 12. 5 d.p.c. mouse embryos showed a high level of expression of EXT1 mRNA in developing limb buds. Epitope tagging experiments revealed the endo plasmic reticulum localization of EXT1 protein. This localization was consistent with a hydrophobic stretch of amino acids present at the N- terminal end of the EXT1 protein. These results provide novel informat ion on the function of EXT1 and the etiology of hereditary multiple ex ostoses. (C) 1998 Academic Press.