| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Department of Molecular Biology, The Lundberg Laboratory, and the 2 Department of Medical Biochemistry, Gothenburg University, Gothenburg, Sweden; the 3 Department of Molecular Medicine and Ophthalmology, St. James’s Hospital, Leeds University, Leeds, United Kingdom; 4 Department of Clinical Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden.
PURPOSE. To evaluate the importance in anterior segment dysgenesis of genetic variation in Foxe3, a gene encoding a forkhead transcription factor specifically expressed in the lens.
METHODS. The phenotype of mice heterozygous for a mutation in the DNA-binding domain of Foxe3 was examined from histologic sections, and DNA binding by the encoded protein was investigated by gel-shift assay. FOXE3 from human patients with Peters’ anomaly was PCR amplified and sequenced.
RESULTS. The dysgenetic lens (dyl) allele of Foxe3 was found to encode a protein unable to bind DNA. Approximately 40% of mice heterozygous for Foxe3dyl have corneal and lenticular defects. The phenotype is variable but typically consists of the equivalent of Peters’ anomaly in humans, with central corneal opacity, keratolenticular adhesion, and, in some cases, anterior polar cataract. In a small cohort (n = 13) of patients with Peters’ anomaly, shown to be normal in the PAX6 locus, one individual was found to be heterozygous for a nonconservative missense mutation in FOXE3. The mutation, which does not occur in 116 chromosomes from a control population, substitutes leucine for arginine 90 at a highly conserved position in the forkhead domain.
CONCLUSIONS. Haploinsufficiency of Foxe3 in a mouse model causes anterior segment dysgenesis similar to Peters’ anomaly. Although causality could not be shown in the human case, the presence of a rare, nonconservative substitution in FOXE3 of a patient with Peters’ anomaly is interesting, in light of the phenotypic similarities with the mutant mice.
This article has been cited by other articles:
|
|
 |
|
  R. Korstanje, J. Desai, G. Lazar, B. King, J. Rollins, M. Spurr, J. Joseph, S. Kadambi, Y. Li, A. Cherry, et al. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects Physiol Genomics, November 1, 2008; 35(3): 296 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zheng, J. Ge, G. Huang, J. Zhang, B. Liu, Y.-M. Hur, and M. He Heritability of Central Corneal Thickness in Chinese: The Guangzhou Twin Eye Study Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4303 - 4307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Matteson, J. Desai, R. Korstanje, G. Lazar, T. E. Borsuk, J. Rollins, S. Kadambi, J. Joseph, T. Rahman, J. Wink, et al. The orphan G protein-coupled receptor, Gpr161, encodes the vacuolated lens locus and controls neurulation and lens development PNAS, February 12, 2008; 105(6): 2088 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Medina-Martinez and M. Jamrich Foxe view of lens development and disease Development, April 15, 2007; 134(8): 1455 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Asai-Coakwell, C. Backhouse, R. J. Casey, P. J. Gage, and O. J. Lehmann Reduced Human and Murine Corneal Thickness in an Axenfeld-Rieger Syndrome Subtype Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4905 - 4909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Evans and P. J. Gage Expression of the homeobox gene Pitx2 in neural crest is required for optic stalk and ocular anterior segment development Hum. Mol. Genet., November 15, 2005; 14(22): 3347 - 3359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Medina-Martinez, I. Brownell, F. Amaya-Manzanares, Q. Hu, R. R. Behringer, and M. Jamrich Severe Defects in Proliferation and Differentiation of Lens Cells in Foxe3 Null Mice Mol. Cell. Biol., October 15, 2005; 25(20): 8854 - 8863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Grewal, J. Stepczynski, R. Kelln, T. Erickson, R. Darrow, L. Barsalou, M. Patterson, D. T. Organisciak, and P. Wong Coordinated Changes in Classes of Ribosomal Protein Gene Expression Is Associated with Light-Induced Retinal Degeneration Invest. Ophthalmol. Vis. Sci., November 1, 2004; 45(11): 3885 - 3895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Wolf, A. Galecki, R. Lipman, S. Chen, M. Smith-Wheelock, D. Burke, and R. Miller Quantitative Trait Locus Mapping for Age-Related Cataract Severity and Synechia Prevalence Using Four-Way Cross Mice Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 1922 - 1929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J. Lehmann, S. Tuft, G. Brice, R. Smith, A. Blixt, R. Bell, B. Johansson, T. Jordan, R. A. Hitchings, P. T. Khaw, et al. Novel Anterior Segment Phenotypes Resulting from Forkhead Gene Alterations: Evidence for Cross-Species Conservation of Function Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2627 - 2633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Yamada, Y. Mizutani-Koseki, T. Hasegawa, N. Osumi, H. Koseki, and N. Takahashi Cell-autonomous involvement of Mab21l1 is essential for lens placode development Development, May 1, 2003; 130(9): 1759 - 1770. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
