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B. Chang, N.L. Hawes, R.E. Hurd, J. Wang, M.T. Davisson, S. Nusinowitz, J.R. Heckenlively; A New Mouse Model of Cone Photoreceptor Function Loss (cpfl6) Associated With the Targeted Hcn1 Gene Mutation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2294.
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© ARVO (1962-2015); The Authors (2016-present)
To report the clinical characterization, genetic analysis and gene identification of a new hereditary model for progressive cone function loss.
While screening mouse strains and stocks at The Jackson Laboratory for genetic mouse models of human ocular disorders, we identified a new mouse model for progressive cone electroretinographic photopic functional loss with cone photoreceptor degeneration. We characterized the clinical effects of this mutation using serial electroretinography (ERG), fundus photography, and histology, and performed genetic analysis including linkage studies.
This new mutation has been named cone photoreceptor function loss 6 (cpfl6) since it is the sixth mutation identified in mice to affect cone function. Mice carrying the cpfl6 mutation show early onset cone electroretinographic photopic functional abnormality. The phenotype can be easily typed by electroretinography at six weeks of age with abnormal cone–mediated photoresponse but normal rod–mediated photoresponses from 6 weeks to 11 months of age. Histological results from mice at parallel ages show an overall normal retinal structure at 2 months of age and a mild peripheral retinal degeneration at 11 months of age. Genetic analysis shows that this disorder is caused by an autosomal recessive mutation that maps to mouse Chromosome 13 closely linked to Hcn1, suggesting that the human homolog may be on Chromosome 5p12. The Hcn1 gene mutation is clearly associated with cpfl6.
The early onset cone electroretinographic photopic functional abnormality combined with our genetic data suggest that this is a new retinal disorder not previously described in mouse or human. Finding a strong association between early onset cone electroretinographic photopic functional abnormality (cpfl6) and hyperpolarization–activated, cyclic nucleotide–gated K+ 1 (Hcn1) mutation is new, and study of HCN1 channels may broaden the understanding of cone photoreceptor functional abnormality.
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