Genetic control of ocular morphogenesis: defective lens development associated with ocular anomalies in C57BL/6 mice.

Congenital ocular defects, including microphthalmia, anophthalmia and cataracts appear in a small proportion (5-15%) of the C57BL/6 inbred strain of laboratory mice. Previous work from this laboratory utilizing C57BL/6 in equilibrium with DBA/2 allophenic (mosaic) mice suggested that the underlying cause of these defects may be a deficiency in C57BL/6 lens development. In these C57BL/6 in equilibrium with DBA/2 allophenic animals, the major proportion of the lens cells were of the DBA/2 strain, in contrast to the other ocular and non-ocular tissues examined where no strain-specific competition was evident. Results presented here reinforce the notion that C57BL/6 lens cells are developmentally retarded. In allophenic combination with another strain, A/J, cells of the C57BL/6 strain were, again, markedly underrepresented in the mosaic lens, whereas no such genotypic specificity was evident in any of the other ocular and non-ocular tissues. Thus, the previous observation of a C57BL/6 deficiency in mosaic lens is more likely a consequence of low C57BL/6 competitiveness rather than some peculiar hyperactivity of the cells of the partner strains. Histological examination of C57BL/6, DBA/2 and A/J pure strain embryos indicated marked differences in the lens development of C57BL/6 embryos compared to the other two strains. For the first 3 days after lens invagination, the cross-sectional areas of DBA/2 lenses were two- to three-fold larger than those of C57BL/6 lenses at comparable stages of development, whereas no comparable difference was noted in the optic cup development in these two strains. This leads to a much higher lens/optic cup size ratio in DBA/2 embryos than C57BL/6 embryos. Scanning electron microscopy also revealed that lens invagination is much less extensive in the C57BL/6 embryos than the A/J embryos. The smaller C57BL/6 lens vesicle also remains deeper in the optic cup than those of the DBA/2 or A/J embryos of comparable developmental age. This is likely to result in the occasional complete envelopment of the entire lens vesicle by the optic cup and lead to arrested ocular development.