Analysis of CRX Protein Profile in the Rdy Cat Model Suggests Molecular Mechanism of Pathology

Abstract

The product of the cone‐rod homeobox gene, CRX, is an important transcription factor critical in the development and maintenance of photoreceptor cells in the retina. Mutations have been document in the human CRX gene that can lead to retinal pathologies such as cone‐rod dystrophy (CoRD). A CRX gene mutation was recently characterized the Rdy (rod‐cone dysplasia) cat, which exhibits an early onset, autosomal dominant disorder modeling human CoRD. A single base deletion in exon 4 resulted in the introduction of a premature stop codon and one‐third of the CRX protein, including the transcriptional transactivation domains, is deleted. A truncated CRX product, as well as the full‐length CRX product, are translated and persist in Rdy individuals as detected through Western blot analysis. Preliminary electrophoretic mobility shift assays suggest that the truncated product binds to the promoter site of feline rhodopsin, likely acting as a competitive inhibitor of the wildtype product. The Rdy cat will provide valuable insights into the mechanisms causative of Rdy disease pathology and is an important animal model of human retinal disease.