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C.F. Inglehearn, H. Tummala, M. Ali, P. Getty, P.M. Hocking, D.W. Burt, D.H. Lester; A Mutation in the Guanine Nucleotide–Binding Protein Beta–3 (Gnb3) Causes Retinal Degeneration and Embryonic Mortality in Chickens . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2298.
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Retinopathy globe enlarged (rge) is a recessive retinal degeneration in chickens which also causes increased embryonic mortality. Affected birds exhibit poor pupillary light response and abnormal behaviour resulting from loss of vision by 3 weeks. Functional vision appears lost by 8 weeks, but ERG amplitudes, which are reduced at hatch, are still measurable at over a year. At one day post–hatch the outer plexiform layer is disorganized and later there is developmental disruption of rod and cone photoreceptor synaptic terminals that progresses with age. A genome–wide screen identified linkage to a 13.7Mb region on chicken chromosome 1. This study aimed to identify the gene and mutation involved
Further linkage analysis using previously uncharacterised microsatellite markers was performed on 138 progeny of an rge/+ and rge/rge cross, and candidate genes were sequenced.
The gene for guanine nucleotide–binding protein beta–3 (GNB3), which encodes a cone transducin beta subunit, was found to have a 3bp deletion (D153del) that segregated with the rge phenotype. This mutation, which deletes a highly conserved aspartic acid residue in the third of seven WD40 repeat domains in GNB3, causes a 70% reduction in immunoreactivity to anti–GNB3 in rge affected retina.
This study illustrates the strength of the chicken as a model for studying human cone disease. GNB3 is implicated as a candidate human retinal dystrophy gene, but mutations were not found in cone–rod and macular dystrophy patients in a previous study. The relatively severe phenotype in rge chickens could implicate a Lebers amaurosis or achromatopsia phenotype. GNB3 is ubiquitously expressed and the c.825C>T GNB3 splicing variant has been associated with hypertension, obesity, diabetes, low birth weight, coronary heart disease and stroke in the human population. Some other functional deficit may therefore cause reduced embryonic viability.
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