A Novel Alternative Spliced Variant of the Transcription Factor AP2alpha is Expressed in the Murine Ocular Lens

The AP2alpha gene encodes a transcription factor containing a basic, helix-span-helix DNA-binding/dimerization domain, which is developmentally regulated and retinoic acid inducible. Recent reports about AP2alpha null mice indicate that AP2alpha plays an important role in embryogenesis, especially in craniofacial development and midline fusion. Ocular development is also affected in these null mice. As AP2alpha may be involved in transcriptional regulation in the lens, it was important to examine the expression of the AP2alpha gene in the lens. Four AP2alpha mRNA variants have been previously isolated from whole mouse embryos. Variants 1, 3, and 4 are transcriptional activators that are transcribed from different promoters and variant 2 is a repressor lacking the activation domain encoded by exon 2. Using in situ-PCR, we found that AP2alpha 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 AP2alpha variants 1, 2, and 3 are expressed in newborn mouse lenses. However, variant 4 is not expressed in the lens. In this report we characterized a novel isoform, which we named variant 5, expressed in the lens and kidney. Variant 5, which is generated by alternative splicing, may function as a repressor due to the partial deletion of the proline-rich transactivation domain encoded by exon 2. This is the first molecular characterization of AP2alpha gene expression in the lens. Our results indicate that two activator and two repressor AP2alpha isoforms may play a role in regulating gene expression in the lens.