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L.S. Hunter, D.J. Sidjanin, G.M. Acland, M. Villagrasa, G.D. Aguirre; Evaluation of PAX6 for Mutations Causing Inherited Ocular Diseases in Canine Models . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2319.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Normal ocular development is dependent on the transcription factor PAX6. Mutations in PAX6 can result in aniridia, cataract, glaucoma, foveal hypoplasia and optic nerve hypoplasia in man. In mice, mutations in Pax6 cause the Small Eyepheonotype characterized by microphthalmia, abnormal lens and iris development and cataract. The purpose of this study is to evaluate the canine PAX6 gene for mutations causal to inherited ocular disease in canine models. Methods: Nine breeds of dog were identified having inherited forms of ocular disease for which PAX6 is a candidate gene. Two affected dogs from each breed were evaluated and their PAX6 sequence compared to canine wildtype sequence. Genomic DNA was prepared from whole blood and exons were scanned using intronic primers. Since the sequence for intron 4 could not be amplified, exon 4 was sequenced using primers in intron 3 and at the 3' end of exon 4, and exon 5 was sequenced using primers at the 5' end of exon 5 and in intron 5. Similarly, because of a homopolymer in the 3'UTR, exon 13 was evaluated using primers in intron 12 and at the 3' end of exon 13. Results: Thirteen exons plus an alternatively spliced exon (5a) are being examined in nine dog breeds with inherited eye diseases including cataracts, microphthalmia, persistent pupillary membranes, rod-cone dysplasia 2, cone-rod dystrophy 1 and 2, and aniridia. To date, no mutations associated with disease have been identified in the exons so far examined including the non-coding exons 1, 2, and 3. In addition to a previously identified SNP in intron 8, a single nucleotide change was identified in exon 7. This was a Cytosine -> Thymine change which did not result in an amino acid change. Microsatellites have been identified in exons 1 and 2, and in introns 6 and 7 which may facilitate linkage analysis. Conclusions: PAX6 plays an integral role in ocular development and mutations in this transcription factor cause different disease phenotypes. Evaluating canine models may identify novel disease phenotypes associated with PAX6 mutations.
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