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Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced by heterozygous mutation of Pax6.
- Source :
-
BMC developmental biology [BMC Dev Biol] 2006 Oct 09; Vol. 6, pp. 46. Date of Electronic Publication: 2006 Oct 09. - Publication Year :
- 2006
-
Abstract
- Background: Knowledge of the consequences of heterozygous mutations of developmentally important genes is important for understanding human genetic disorders. The Gli3 gene encodes a zinc finger transcription factor and homozygous loss-of-function mutations of Gli3 are lethal. Humans heterozygous for mutations in this gene suffer Greig cephalopolysyndactyly or Pallister-Hall syndromes, in which limb defects are prominent, and mice heterozygous for similar mutations have extra digits. Here we examined whether eye development, which is abnormal in mice lacking functional Gli3, is defective in Gli3+/- mice.<br />Results: We showed that Gli3 is expressed in the developing eye but that Gli3+/- mice have only very subtle eye defects. We then generated mice compound heterozygous for mutations in both Gli3 and Pax6, which encodes another developmentally important transcription factor known to be crucial for eye development. Pax6+/-; Gli3+/- eyes were compared to the eyes of wild-type, Pax6+/- or Gli3+/- siblings. They exhibited a range of abnormalities of the retina, iris, lens and cornea that was more extensive than in single Gli3+/- or Pax6+/- mutants or than would be predicted by addition of their phenotypes.<br />Conclusion: These findings indicate that heterozygous mutations of Gli3 can impact on eye development. The importance of a normal Gli3 gene dosage becomes greater in the absence of a normal Pax6 gene dosage, suggesting that the two genes co-operate during eye morphogenesis.
- Subjects :
- Animals
Cornea abnormalities
Cornea growth & development
Cornea metabolism
Eye embryology
Eye growth & development
Eye metabolism
Female
Gene Expression Regulation, Developmental
Genotype
Heterozygote
Male
Mice
Mice, Inbred C57BL
PAX6 Transcription Factor
Penetrance
Phenotype
RNA, Messenger genetics
RNA, Messenger metabolism
Retina abnormalities
Retina growth & development
Retina metabolism
Zinc Finger Protein Gli3
Eye Abnormalities genetics
Eye Proteins genetics
Homeodomain Proteins genetics
Kruppel-Like Transcription Factors genetics
Mutation genetics
Nerve Tissue Proteins genetics
Paired Box Transcription Factors genetics
Repressor Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1471-213X
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- BMC developmental biology
- Publication Type :
- Academic Journal
- Accession number :
- 17029624
- Full Text :
- https://doi.org/10.1186/1471-213X-6-46