Enlargement of the globe with ocular malformations in c-Myc transgenic mice

Purpose: To study the ocular development in transgenic mice carrying the mouse c-myc gene under the control of the Mx gene promoter (Mx-c-myc). Methods: Transgenic mice were generated by standard techniques. Far histological studies, the tissues were fixed with 10% buffered formalin, embedded in paraffin according to the standard procedure and sliced in 4-mu m sections, c-Myc expression was investigated by reverse transcriptase-polymerase chain reaction and Southern blot analysis. Results: A line of the Mx-c-myc mice displayed progressive enlargement of the globe with other ocular malformations. Histologically, the enlarged eyes exhibited closed cornea-iris angle, microphakia, corneal epithelial disorders, and attenuation of the inner retinal layers. Developmental analysis of eyes from these Mx-c-myc mice revealed irregular development of the iris and ciliary body at embryonic day 15.5 and the closed angle at 1 week of age. Leaky exogenous c-myc expression was detected in cornea, iris, lens, and retina from the Mx-c-myc mice by reverse transcriptase-polymerase chain reaction and Southern blot analysis. No other developmental abnormalities were observed in the Mx-c-myc mice. The anterior segment of the enlarged eyes showed the closed angle with elongation of the iris and ciliary body. There was no attenuation in the outer retinal layers from the outer plexiform layer to the retinal pigment epithelium. Conclusions: We conclude that the buphthalmos and accompanying changes were not due to expression of the exogenous c-myc in cornea and retina but may be the secondary changes of elevated intraocular pressure. We suggest that Mx-c-myc mice can serve as a useful model for investigating the development of the anterior segment and the genesis of buphthalmos. Jpn J Ophthalmol 1999;43:201-208 (C) 1999 Japanese Ophthalmological Society.