OCULAR PATHOLOGY IN MICE WITH A TRANSGENIC INSERTION AT THE MICROPHTHALMIA LOCUS

A DNA insertional mutation at the microphthalmia locus (mi) in a trans genic mouse has been developed and given the allele symbol of mi(tg) ( Krakowsky et al., 1993). Mice homozygous for this transgene have eyes markedly reduced in size and relatively unpigmented. In this study, we examined the morphology of these eyes using light and electron micros copy. Transgenic homozygous (mi(tg)/mi(tg)) animals have a structurall y normal choroid which lacks melanocytes but contains occasional leuko cytes, The elastica of Bruch's membrane is absent except in an occasio nal site. The retinal pigmented epithelium (RPE) appears dramatically abnormal. It displays cellular heterogeneity, residual basal infolding s and apical microvilli, rare and immature melanosomes, and numerous c ilia-like structures. Occasionally, cells of the RPE appear to have ex truded into or from the choroid. The photoreceptor cells are devoid co mpletely of outer segments and partially of inner segments. Numerous a ctive macrophages are present between the amelanotic RPE and neuro-ret ina and also within the vitreous body. The anterior uveal tract is und erdeveloped and hypomelanotic. This new microphthalmia model exhibits ocular pathology with similarities and differences to other mutations and the mi (microphthalmia) locus.