Lens crystallins and their genes: diversity and tissue-specific expression.

The soluble proteins--or crystallins--that constitute the bulk of the cellular, transparent eye lens are encoded by a surprisingly diverse group of genes. Several crystallin genes generate further heterogeneity by producing more than one polypeptide, in which they use different mechanisms. Some crystallin genes are lens specific (e.g., alpha A and gamma), while others show only lens preference (alpha B and enzyme/crystallins); all the crystallin genes are temporally and spatially regulated in the developing lens. Transfection and transgenic mouse experiments, identifying DNA regulatory elements in the 5' flanking region and in one case (delta) in an intron, point to transcriptional control as the primary basis for the tissue- and differentiation-specific expression of crystallin genes. Crystallin promoters have been used to target foreign genes to the lens in transgenic and chimeric mice. Such gene transfer experiments have been used to create tumors and ablate specific cells in the lens. The identification of trans-acting factors responsible for crystallin gene expression has begun but is in its infancy. The many mechanisms leading to the diversity and precise regulation of crystallins show that the lens is, in addition to a favorable tissue for studying differential gene expression, a fascinating portrait of molecular evolution.