LOCALIZATION OF TYPE-II COLLAGEN MESSENGER-RNA ISOFORMS IN THE DEVELOPING EYES OF NORMAL AND TRANSGENIC MICE WITH A MUTATION IN TYPE-II COLLAGEN GENE

Purpose. To elucidate the function of type II collagen in the developm ent and diseases of the eye by analyzing the temporospatial expression of the long (IIA) and short (IIB) isoforms of type II collagen in the normal and transgenic Dell mice. Methods. Normal and Deli transgenic embryos harboring a deletion mutation in the pro alpha 1 (II) collagen chain were studied from day 10.5 of embryonic development up to day 1 0 postpartum. Northern and in situ hybridizations and RNase protection assays were used to study the developmental and temporospatial expres sion of type II collagen isoforms. Results. Expression of type II coll agen mRNAs was observed at all developmental stages with maximum expre ssion at 16.5 days of embryonic development. RNase protection analyses confirmed that both wild type and transgene-derived mRNAs underwent s imilar alternative splicing of exon 2 in the eye. By in situ hybridiza tion, both isoforms were observed in the cornea, sclera, vitreous, gan glion cell layer of retina, developing ciliary body-iris, and in the r etinal pigment epithelium-Bruch's membrane as well as in the lens and conjunctiva. Differences were observed between eyes of Deli mice and o f control subjects in the levels and temporal expression patterns of t ype II collagen mRNA, which resulted in structural abnormalities in hi stologic analysis. Conclusions. Widespread expression of type II colla gen mRNAs in ocular structures suggests an important rule for type II collagen in structural development of the eye. As the expression patte rns observed correspond to structural abnormalities in the eyes of Del l mice, the current results offer a promising basis for further develo pment of mouse models for arthroophthalmopathies.