Journal article
Bestrophin gene mutations cause canine multifocal retinopathy: a novel animal model for best disease
Investigative ophthalmology & visual science, Vol.48(5), pp.1959-1967
05/2007
DOI: 10.1167/iovs.06-1374
PMCID: PMC1931491
PMID: 17460247
Abstract
Canine multifocal retinopathy (cmr) is an autosomal recessive disorder of multiple dog breeds. The disease shares a number of clinical and pathologic similarities with Best macular dystrophy (BMD), and cmr is proposed as a new large animal model for Best disease. cmr was characterized by ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1 (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid 5'- and 3'-RACE. Expression of the canine gene transcripts and protein was analyzed by Northern and Western blotting and immunocytochemistry. All exons and the flanking splice junctions were screened by direct sequencing. The clinical phenotype and pathology of cmr closely resemble lesions of BMD. Canine VMD2 spans 13.7 kb of genomic DNA on CFA18 and shows a high level of conservation among eukaryotes. The transcript is predominantly expressed in RPE/choroid and encodes bestrophin, a 580-amino acid protein of 66 kDa. Immunocytochemistry of normal canine retina demonstrated specific localization of protein to the RPE basolateral plasma membranes. Two disease-specific sequence alterations were identified in the canine VMD2 gene: a C(73)T stop mutation in cmr1 and a G(482)A missense mutation in cmr2. The authors propose these two spontaneous mutations in the canine VMD2 gene, which cause cmr, as the first naturally occurring animal model of BMD. Further development of the cmr models will permit elucidation of the complex molecular mechanism of these retinopathies and the development of potential therapies.
Details
- Title: Subtitle
- Bestrophin gene mutations cause canine multifocal retinopathy: a novel animal model for best disease
- Creators
- Karina E Guziewicz - Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USABarbara ZangerlSarah J LindauerRobert F MullinsLynne S SandmeyerBruce H GrahnEdwin M StoneGregory M AclandGustavo D Aguirre
- Resource Type
- Journal article
- Publication Details
- Investigative ophthalmology & visual science, Vol.48(5), pp.1959-1967
- DOI
- 10.1167/iovs.06-1374
- PMID
- 17460247
- PMCID
- PMC1931491
- NLM abbreviation
- Invest Ophthalmol Vis Sci
- ISSN
- 0146-0404
- eISSN
- 1552-5783
- Publisher
- United States
- Grant note
- R03 EY014563-03 / NEI NIH HHS R01 EY013132-02 / NEI NIH HHS R01 EY006855-19 / NEI NIH HHS P30 EY001583-25 / NEI NIH HHS R01 EY006855-15 / NEI NIH HHS R03 EY014563 / NEI NIH HHS R01 EY013132-06 / NEI NIH HHS P30 EY-001583 / NEI NIH HHS R01 EY013132-03 / NEI NIH HHS P30 EY001583 / NEI NIH HHS R01 EY013132-07 / NEI NIH HHS R01 EY006855-16 / NEI NIH HHS R01 EY013132-04 / NEI NIH HHS R03 EY014563-01 / NEI NIH HHS R01 EY006855-21 / NEI NIH HHS R01 EY006855-17 / NEI NIH HHS EY13132 / NEI NIH HHS R01 EY006855-13 / NEI NIH HHS R01 EY013132-05 / NEI NIH HHS R01 EY013132 / NEI NIH HHS R03 EY014563-02 / NEI NIH HHS R01 EY006855 / NEI NIH HHS EY06855 / NEI NIH HHS R01 EY013132-04S1 / NEI NIH HHS R01 EY006855-20 / NEI NIH HHS R01 EY006855-18 / NEI NIH HHS R01 EY013132-01 / NEI NIH HHS R01 EY017451 / NEI NIH HHS R01 EY006855-14 / NEI NIH HHS
- Language
- English
- Date published
- 05/2007
- Academic Unit
- Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980086502771
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