Relationship of Pax6 activity levels to the extent of eye development in the mouse, Mus musculus

In the present study we extend the mouse Pax6 mutant allelic series to include a homozygous and hemizygous viable hypomorph allele. The Pax6^132-14Neu allele is a p.Phe272Ile missense mutation within the third helix of the homeodomain. The mutant Pax6 homeodomain shows greatly reduced binding activity to the P3 DNA binding target. Glucagon promoter activation by the entire mutant Pax6 product of a reporter gene driven by the G1 paired and homeodomain DNA binding target was slightly increased. We constructed mutant Pax6 genotypes such that Pax6 activity ranged between 100% and 0%, and show that the extent of eye development is progressively reduced as Pax6 activity decreased. Two apparent thresholds identify three groups in which the extent of eye development abruptly shifted from complete eye at the highest levels of Pax6, to a rudimentary eye at intermediate levels of Pax6, to very early termination of eye development at the lowest levels of Pax6. Of the two Pax6-positive regions which participate in eye development, the surface ectoderm, which develops into the lens vesicle and the cornea, is more sensitive to reduced levels of Pax6 activity than the optic vesicle, which develops into the inner and outer retinal layers.

Key Words: Mouse, Pax6, allelic series, eye development, hypomorph mutation

Online ISS 1091-6490
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