A NOVEL ALTERNATIVE SPLICED VARIANT OF THE TRANSCRIPTION FACTOR AP2-ALPHA IS EXPRESSED IN THE MURINE OCULAR LENS

The AP2 alpha gene encodes a transcription factor containing a basic, helix-span-helix DNA-binding/dimerization domain, which is development ally regulated and retinoic acid inducible. Recent reports about AP2 a lpha null mice indicate that AP2 alpha plays an important role in embr yogenesis, especially in craniofacial development and midline fusion. Ocular development is also affected in these null mice. As AP2 alpha m ay be involved in transcriptional regulation in the lens, it was impor tant to examine the expression of the AP2 alpha gene in the lens. Flou r AP2 alpha mRNA variants have been previously isolated from whole mou se embryos. Variants 1, 3, and 4 are transcriptional activators that a re transcribed from different promoters and variant 2 is a repressor l acking the activation domain encoded by exon 2. Using in situ-PCR, we found that AP2 alpha is expressed in the lens epithelia but not in the lens fibers. RT-PCR analysis of lens mRNA with amplimers specific for each variant revealed that AP2 alpha variants 1, 2, and 3 are express ed ill newborn mouse lenses. However, variant 4 is not expressed in th e lens. In this report we characterized a novel isoform, which we name d variant 5, expressed in the lens and kidney. Variant 5, which is gen erated by alternative splicing, may function as a repressor due to the partial deletion of the proline-rich transactivation domain encoded b y exon 2. This is the first molecular characterization of AP2 alpha ge ne expression in the lens. Our results indicate that two activator and two repressor AP2 alpha isoforms may play a role in regulating gene e xpression in the lens. (C) 1998 Academic Press.