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Iris hypoplasia in mice that lack the alternatively spliced Pax6(5a) isoform
Sanjaya Singh1, Rajnikant Mishra, Nelson A Arango
1Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Abstract:
PAX6 is an evolutionarily conserved transcription factor that plays a critical role in vertebrate and invertebrate eye formation. Heterozygous null mutations in the PAX6 gene result in aniridia in humans and a distinct small eye syndrome in rodents. Vertebrates primarily express two alternatively spliced isoforms of Pax6 that differ by the presence or absence of exon 5a (e5A) that encodes an additional 14 aa residues within the paired domain. The e5a-containing isoform, PAX6(5a), is specific to and conserved in vertebrates. To determine the role of PAX6(5a), we have generated mice that lack e5a of the Pax6 gene. Unlike Pax6 null mice that exhibit anopthalmia with central nervous system defects and lethality, 5a isoform-null mice have iris hypoplasia and defects in the cornea, lens, and retina. Although invertebrates have structures that respond to light intensity and act to restrict light exposure of the eyes, a significant and distinct feature of the vertebrate eye is its ability to regulate the amount of incoming light through contractile pupils. This feature of the eye not only allows vertebrates to see in various light conditions but also enhances image resolution. The requirement of the 5a isoform in iris formation suggests that the evolution of this isoform contributed to advanced features of the vertebrate eye.
Insights
The PAX6(5a) isoform is crucial for vertebrate eye development, specifically iris formation. Its absence causes iris hypoplasia and other eye defects, suggesting its role in advanced vertebrate vision.
Area of Science:
- Developmental Biology
- Evolutionary Biology
- Genetics
Background:
- PAX6 is a conserved transcription factor essential for eye development in vertebrates and invertebrates.
- Mutations in PAX6 cause aniridia in humans and small eye syndrome in rodents.
- Vertebrates express two Pax6 isoforms, differing by exon 5a (e5A), which encodes 14 amino acids in the paired domain.
Purpose of the Study:
- To investigate the specific role of the PAX6(5a) isoform in eye development.
- To determine the function of the e5A-containing isoform, which is unique to vertebrates.
Main Methods:
- Generation of mice lacking the e5A exon of the Pax6 gene.
- Phenotypic analysis of these 5a isoform-null mice, comparing them to Pax6 null mice.
Main Results:
- Pax6 null mice exhibit anophthalmia, CNS defects, and lethality.
- Mice lacking the 5a isoform (5a isoform-null) display iris hypoplasia, and defects in the cornea, lens, and retina.
- Unlike invertebrates, vertebrates possess contractile pupils for light regulation, a feature linked to the 5a isoform's role in iris formation.
Conclusions:
- The PAX6(5a) isoform is essential for proper iris development in vertebrates.
- The evolution of the 5a isoform likely contributed to advanced vertebrate eye features, such as pupil regulation.
- This isoform plays a critical role in adapting vision to various light conditions and enhancing image resolution.