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PMID: 18562673 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Genetics ·Vol. 179 ·No. 3 ·2008-07-00 ·Pages 1345-55

Favor J, Gloeckner CJ, Neuhäuser-Klaus A, Pretsch W, Sandulache R, Saule S, Zaus I

Abstract

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.

MeSH Terms
Animals Breeding Chromosome Mapping DNA/metabolism Eye/embryology Eye Proteins/genetics,metabolism Female Fertility Gene Expression Regulation, Developmental Genotype Glucagon/genetics Heterozygote Homeodomain Proteins/genetics,metabolism Male Mice Mice, Mutant Strains Organ Size PAX6 Transcription Factor Paired Box Transcription Factors/genetics,metabolism Phenotype Promoter Regions, Genetic/genetics Protein Binding Repressor Proteins/genetics,metabolism
Chemicals
Eye Proteins Homeodomain Proteins PAX6 Transcription Factor PAX6 protein, human Paired Box Transcription Factors Pax6 protein, mouse Repressor Proteins DNA Glucagon
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Favor Jack
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany. [email protected]
Gloeckner Christian Johannes
Neuhäuser-Klaus Angelika
Pretsch Walter
Sandulache Rodica
Saule Simon
Zaus Irmgard
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1534/genetics.108.088591
Email
[email protected]
Published
2008-07-00
Epub
2008-00-18
Pages
1345-55
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC2475738
Subset
IM
Grants
NEI NIH HHS · R0-1EY10321 · United States
External Links
PubMed source DOI: 10.1534/genetics.108.088591 PMC Full Text View journal details
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