Journal article
Lyst mutation in mice recapitulates iris defects of human exfoliation syndrome
Investigative ophthalmology & visual science, Vol.50(3), pp.1205-1214
03/2009
DOI: 10.1167/iovs.08-2791
PMCID: PMC2693230
PMID: 19029039
Abstract
Human eyes with exfoliation syndrome (XFS) exhibit a distinctive pattern of iris transillumination defects that are recapitulated in Lyst mutant mice carrying the beige allele. The purpose of this study was to determine the anatomic basis for Lyst-mediated transillumination defects, test whether Lyst mutant mice develop other features of XFS, and describe the molecular basis of the beige mutation. Lyst mutant mice and strain-matched controls were compared by clinical, histologic, immunohistochemical, and molecular genetic analyses. Slit-lamp examination showed that Lyst mutant mice uniformly exhibit XFS-like transillumination defects. Histologic analysis showed that these defects correlate with a sawtooth morphology of the iris pigment epithelium. Lyst mutant mice also produce an exfoliative-like material and exhibit pronounced pigment dispersion. Despite these insults, Lyst mutation does not cause increased intraocular pressure or optic nerve damage in the C57BL/6J genetic background. Sequence analysis identified that the beige mutation is predicted to delete a single isoleucine from the WD40 domain of the LYST protein, suggesting that this mutation is likely to disrupt a protein-protein interaction. Lyst mutant eyes exhibit multiple features of XFS. Recent human genetic association studies have identified changes occurring in the LOXL1 gene as an important risk factor for XFS but also indicated that other factors contributing to risk likely exist. These results demonstrated that mutation of the Lyst gene can produce ocular features of human XFS and suggested that LYST or LYST-interacting genes may contribute to XFS.
Details
- Title: Subtitle
- Lyst mutation in mice recapitulates iris defects of human exfoliation syndrome
- Creators
- Colleen M Trantow - Department of Molecular Physiology, University of Iowa, Iowa City, Iowa 52242, USAMao MaoGreg E PetersenErin M AlwardWallace L M AlwardJohn H FingertMichael G Anderson
- Resource Type
- Journal article
- Publication Details
- Investigative ophthalmology & visual science, Vol.50(3), pp.1205-1214
- Publisher
- United States
- DOI
- 10.1167/iovs.08-2791
- PMID
- 19029039
- PMCID
- PMC2693230
- ISSN
- 0146-0404
- eISSN
- 1552-5783
- Grant note
- EY017673 / NEI NIH HHS R01 EY017673-01A2 / NEI NIH HHS R01 EY017673 / NEI NIH HHS
- Language
- English
- Date published
- 03/2009
- Academic Unit
- Molecular Physiology and Biophysics; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980289402771
Metrics
34 Record Views