XI型コラーゲンα2鎖遺伝子の転写制御領域の解析

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Type XI collagen constitutes the cartilage extracellular matrix and plays an important role in skeletal development. To understand the molecular mechanisms controlling expression of type XI collagen, we investigated the promotor region of the mouse α2(XI)collagen gene(Collla2). We also created transgenic mice bearing various fragments of the promotor and the first intron of Collla2 linked to the Escherichia coli β-galactosidase reporter gene to identify the cis-acting elements responsible for tissue- and site-specific expression during development. Analysis of the primary structure of the 5' flanking region of Collla2 indicated that the retinoid X receptor β gene was located 742 bp upstream of the transcriptional start site of Collla2. From these results, the promotor region of Collla2 appeared to be localized within this 742 bp sequence, which contained multiple consensus sequences for transcriptional factors. Examination of the transgenic mice revealed that the DNA construct contained the entire 742 bp promoter which directs lacZ expression in the primodial cartilage of long bones of limbs and ribs. On the other hand, deletion of upstream 289 bp resulted in the loss of specific expression. The spatiotemporal profile of expression directed by the -742 bp promoter was not identical to that of the endogenous α2(XI)collagen gene. Specifically, transgenic mice did not express the transgene in the notochord and the transgene was also distinctly inactive in the primodial cartilage of the vertebral bodies and of small bones including the carpals and tarsals. Addition of the first intron sequence to the entire promoter resulted in expression in the notochord and all of cartilaginous tissues(including the carpals, tarsals and vertebral bodies), with a pattern of expression mimicking that of endogenous Collla2 mRNA. Addition of the intron sequence to the short promoter sequence led to expression in the notochord and primodial cartilage of long bones in limbs and ribs, but not in primordial cartilage of carpals, tarsals and vertebral bodies. These results indicate that the necessary elements conferring tissue-specific expression in mouse embryos reside in the upstream 742 bp and first intron segments of the mouse Collla2 gene. Our results also suggest the presence of site-specific cis-acting elements in the regulatory region of Collla2 which control gene expression in different cartilaginous components of the skeleton.
日本結合組織学会の論文
1998-03-25

XI型コラーゲンα2鎖遺伝子の転写制御領域の解析

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