Crystallins, which have been recruited from stress proteins and enzymes, generally maintain dual roles without gene duplication. The gene recruitment of orthoquinone reductase/zeta-crystallin has occurred through the use of alternative promoters. We have analyzed the putative lens promoter of this gene showing that discrete regions confer lens preference, while upstream positive and negative elements confer improved lens specificity. The rapid amplification of cDNA ends (RACE) polymerase chain reaction (PCR) technique has been used to show that delta1, delta2, and epsilon-crystallins use the same promoters for lens and nonlens expression. The duck tau-crystallin gene has been introduced into transgenic mice to study expression in lens. The cDNA for mu- crystallin, a mammalian taxon-specific crystallin, has been cloned. mu- Crystallin is a mammalian homologue of bacterial ornithine cyclodeaminases. Outside the lens, mu is expressed in the retina and brain, and we have cloned human retina mu. In the developing chick retina, mu is preferentially associated with photoreceptors. We have continued to analyze the expression and function of growth factors and other proteins that have roles in lens differentiation. The coordination of lens 10K/major intrinsic factor (MIF) with differentiation has been established. Furthermore, we have found that total mouse lens extract has MIF activity, suggesting that it could play a role in lens-induced eye inflammation. The cloning of the human 10K/MIF gene is under way. We have also found that transforming growth factor beta (TGF-beta) may play a role in regulating 10K/MIF expression.
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