Embryology and morphology of microphthalmia in transgenic mice expressing a gamma F-crystallin/diphtheria toxin A hybrid gene.

BACKGROUND

Transgenic mice in which elongating lens fiber cells were ablated resulting in microphthalmia have been reported, however, their embryology and detailed morphology have not.

EXPERIMENTAL DESIGN

The morphology of homozygous and hemizygous CDI, transgenic mice carrying the gamma FDT-A gene was studied by light microscopy on different days of gestation as well as postpartum. The findings were compared with normal CD-1 wild type controls.

RESULTS

The earliest changes in mouse embryos transgenic for the gamma F-crystallin/diphtheria toxin A transgene are seen on day 12, when apoptotic cells appear in the area of elongation. In hemizygous embryos, ocular development is relatively normal until day 17 when the lens and eye are slightly smaller than normal and the lens vesicle is filled with abnormal lens material. At this time, the posterior capsule of the lens may rupture, releasing abnormal lens material which disperses throughout the eye, perturbing growth and other ocular structures. Additional breaks may subsequently occur and the ultimate morphology of the hemizygotes correlates with when the posterior capsule ruptures, how much lens material is released, and where it disperses. In homozygous embryos, due to extensive ablation of lens fiber cells, the "lens" becomes a diminutive mass of abnormal lens material, posteriorly located within the eye, and otherwise unable to fulfill its mechanical or inductive role in the development of the cornea, anterior chamber, iris, ciliary epithelium, and zonules with the result that all of these structures are markedly abnormal or absent. In addition, the lens is necessary for the accumulation of vitreous which in turn is required for the growth of the eye as a whole. In homozygous animals, vitreous does not accumulate and severe microphthalmia results.

CONCLUSIONS

This study confirms and extends previous observations and conclusions on the central, orchestrating role of the lens in the development of the eye and illustrates the power of transgenic technology to elucidate the finer points of mammalian ocular development.