EXPRESSION OF TYPE-II AND TYPE-IX COLLAGEN ISOFORMS DURING NORMAL ANDPATHOLOGICAL CARTILAGE AND EYE DEVELOPMENT

Cartilage collagens type II and type IX exist in two alternative forms which arise from alternative splicing and alternative use of promoter s, respectively In the present study we analyzed temporal and spatial expression patterns of the two isoforms of type II and type IX collage n transcripts as well as those of alpha 2(IX) and alpha 3(IX) collagen mRNAs in limb cartilages and eyes during mouse embryonic development. Northern and RNase protection assays revealed temporal coregulation o f the two alternative isoforms in limbs, but not in the eye where no l ong form of alpha 1(IX) collagen mRNA was detected. Although in situ h ybridization of limbs revealed identical expression patterns of the lo ng form of type II collagen and the short form of alpha 1(IX) collagen mRNA in the perichondrium and periosteum of 14.5-18.5-day embryos, th e patterns were distinctly different at day 12.5 of development: the l ong form of type II collagen mRNA was expressed throughout the develop ing cartilaginous anlage whereas the short form of alpha 1(TX) collage n mRNA was expressed in the surrounding mesenchyme. Some differences w ere also detected in the temporal and spatial expression patterns betw een the alpha 1(IX), alpha 2(IX), and alpha 3(IX) collagen mRNAs. In t he eyes, alpha 2(IX) collagen mRNA had highest expression levels at da y 12.5, whereas alpha 1(IX) and a3(IX) collagen mRNAs peaked later, at day 16.5. In the limbs, alpha 1(IX) and alpha 3(IX), but not alpha 2( IX), collagen mRNAs were detected in periosteal cells after 16.5 days of development. In transgenic Del1 mice, harboring type II collagen tr ansgenes with a small deletion mutation, expression of mutant mRNA aff ected neither the alternative splicing of wild-type or mutant transcri pts nor the ratio of the two alternative forms of the alpha 1(IX) coll agen mRNA. Despite some distinct similarities, the two alternative for ms of type II and type IX collagen must, therefore, be under different ial control during mouse development.