Functional Properties of Natural Human PAX6 and PAX6(5a) Mutants

Pax6 is essential for development of the eye, brain, and pancreas. Two major products of PAX6 are specific DNA-binding proteins, PAX6 and PAX6(5a). PAX6(5a) contains a short insertion influencing its DNA-binding activity. Heterozygous mutations in PAX6 result in abnormal eye development implicating haploinsufficiency. Deletions of one PAX6 allele result in aniridia characterized by severe ocular phenotypes. Approximately 10% of PAX6 mutations encode missense mutations. These mutations usually cause less severe abnormalities than does aniridia. The moderate phenotypes raise the possibility that different ocular tissues are differently sensitive to specific mutations. To test this hypothesis, we probed functional properties of individual mutated Pax6 proteins in a variety of conditions.