Expression of Sox9 and Type IIA Procollagen during Ocular Development and Aging in Transgenic Del1 Mice with a Mutation in the Type II Collagen Gene

Abstract

Purpose

To study the expression and distribution of transcription factor Sox9 and type IIA procollagen in the developing and aging eyes of normal and transgenic Del1 mice carrying proa1(II) collagen transgenes with a short deletion mutation, which cause ocular abnormalities in this mouse line.

Methods

The eyes of Del1 mice were studied on embryonic days E14.5, E16.5 and E18.5, and at the ages of 4 and nine months, using their nontransgenic littermates as controls. Sox9 and proa1(IIA) collagen were detected by RNase protection assay and immunohistochemistry.

Results

RNase protection assay revealed Sox9 transcripts in the eyes of Del1 and control mice during development and aging. The mRNA for type IIA procollagen had a similar temporal expression pattern. On embryonic days E14.5, E16.5 and E18.5, Sox9 was located by immunohistochemistry in the nuclei and type IIA procollagen in the extracellular space of the developing retina. During growth and aging, the ocular expression of Sox9 mRNA and the immunohistochemical reaction for Sox9 antibody diminished, concomitant with the reduction in type II procollagen mRNA. However, at the age of nine months, levels of Sox9 and type IIA procollagen mRNAs were higher in the degenerating eyes of Del1 and control mice.

Conclusions

The similarities in the temporo-spatial distribution of Sox9 and type IIA procollagen suggest that this transcription factor is involved in the activation of type II collagen expression in the eye, as has been demonstrated in prechondrogenic mesenchyme and immature cartilage. The increased production of Sox9 and type IIA procollagen in the aging retina and vitreous is analogous to degenerating articular cartilage where attempted tissue repair has also been observed.