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.
Robinson
M L
ML
Department of Biological Sciences, University of South Carolina, Columbia 29208.
Holmgren
A
A
Dewey
M J
MJ
D000818:Animals; D005124:Eye Abnormalities / Q000196:embryology / Q000235:genetics*; D007908:Lens, Crystalline / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009024:Morphogenesis / Q000235:genetics; D009030:Mosaicism