Influence of PAX6 gene dosage on development: overexpression causes severe eye abnormalities

Item Type:	Article
Title:	Influence of PAX6 gene dosage on development: overexpression causes severe eye abnormalities
Creators Name:	Schedl, A. and Ross, A. and Lee, M. and Engelkamp, D. and Rashbass, P. and van Heyningen, V. and Hastie, N.D.
Abstract:	Aniridia in man and Small eye in mice are semidominant developmental disorders caused by mutations within the paired box gene PAX6. Whereas heterozygotes suffer from iris hypoplasia, homozygous mice lack eyes and nasal cavities and exhibit brain abnormalities. To investigate the role of gene dosage in more detail, we have generated yeast artificial chromosome transgenic mice carrying the human PAX6 locus. When crossed onto the Small eye background, the transgene rescues the mutant phenotype. Strikingly, mice carrying multiple copies on a wild-type background show specific developmental abnormalities of the eye, but not of other tissues expressing the gene. Thus, at least five different eye phenotypes are associated with changes in PAX6 expression. We provide evidence that not only reduced, but also increased levels of transcriptional regulators can cause developmental defects.
Keywords:	Base Sequence, DNA-Binding Proteins, Eye Abnormalities, Eye Proteins, Gene Dosage, Developmental Gene Expression Regulation, Genetic Complementation Test, Homeodomain Proteins, Fluorescence In Situ Hybridization, Molecular Sequence Data, Paired Box Transcription Factors, Phenotype, Repressor Proteins, Transgenes, Animals, Mice
Source:	Cell
ISSN:	0092-8674
Publisher:	Cell Press
Volume:	86
Number:	1
Page Range:	71-82
Date:	12 July 1996
Official Publication:	https://doi.org/10.1016/S0092-8674(00)80078-1
PubMed:	View item in PubMed

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