Relationship of Pax6 Activity Levels to the Extent of Eye Development in the Mouse, Mus musculus

In this 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 Phe272Ile missense mutation within the third helix of the homeodomain. The mutant Pax6 homeodomain shows greatly reduced binding activity to th...

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Bibliographic Details
Published in:Genetics (Austin) 2008-07, Vol.179 (3), p.1345-1355
Main Authors: Favor, Jack, Gloeckner, Christian Johannes, Neuhauser-Klaus, Angelika, Pretsch, Walter, Sandulache, Rodica, Saule, Simon, Zaus, Irmgard
Format: Article
Language:English
Subjects:
Amino acids
Animals
Breeding
Chromosome Mapping
DNA - metabolism
Eye - embryology
Eye Proteins - genetics
Eye Proteins - metabolism
Female
Fertility
Gene Expression Regulation, Developmental
Genes
Genetics
Genotype
Genotype & phenotype
Glucagon - genetics
Heterozygote
Histology
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Investigations
Male
Mice
Mice, Mutant Strains
Mutation
Organ Size
Paired Box Transcription Factors - genetics
Paired Box Transcription Factors - metabolism
PAX6 Transcription Factor
Phenotype
Pituitary gland
Promoter Regions, Genetic - genetics
Protein Binding
Repressor Proteins - genetics
Repressor Proteins - metabolism
Studies
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Summary:In this 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 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 that 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.
ISSN:0016-6731
1943-2631
1943-2631
DOI:10.1534/genetics.108.088591