Screening for mouse eye and vision defects at MRC Harwell

Purpose Characterisation of novel genes involved in vision and eye development from the Harwell EUMODIC screen and a recessive ENU mutagenesis screen. Methods Mice have been generated through the EuComm and EuModic programmes that have knockout mutations in defined genes. In addition, mice with random, undefined, mutations have been produced by chemical mutagenesis. Cohorts of these mice have been subjected to slit lamp examination and indirect ophthalmoscopy, and are tested for visual function using a virtual optokinetic drum with a computer generated image displayed around the test animal. Further phenotypic characterisation involves histology and use of tissue markers. In order to preserve the three‐dimensional structure of the eye for examination of the vasculature, for example, we are exploring the use of Optical Projection Tomography which images the intact eye and allows reconstruction of eye structure. Results We have identified a number of mouse lines defective in the visual system. These defects include microphthalmia, eyes open at birth, lens, cornea or iris defects, intraocular bleeding, and retinal degeneration. Furthermore, one line exhibits persistent fetal vasculature in the vitreous (PHPV) which normally regresses after birth through the action of resident macrophages. Determining the basis of this phenotype involves analysis of both the embryonic and adult eye, since mice with defective optic‐fissure closure have also been described with this phenotype. Conclusion Characterisation of these mutant lines will enable us to contribute to a more comprehensive understanding of the genetic regulation of eye development and tissue maintenance within the visual system. Many of these mutants are valuable genetic models of human eye diseases.