9 10The rd phenotype is caused by a null mutation in the photoreceptor guanylate cyclase ( Gucy2d) gene and is thus a model for Leber congenital amaurosis. These are the Rhode Island Red strain rd, 3blindness enlarged globe ( beg), 4retinal dysplasia and degeneration ( rdd), 5 6 7delayed amelanotic strain DAM, 8and retinopathy globe enlarged ( rge). Nevertheless, five forms of hereditary retinal degeneration have been reported in the chicken. In contrast, the chicken has been underused as a model for human inherited disease. Furthermore, the chicken has served for many years as a useful developmental model, particularly for the formation of the eye (see, for example, Fokina and Frolova 2 ). The chicken genome was the first of the taxonomic class Aves (Birds) to be sequenced, 1and now many resources are available to support genetic research in chickens (). It therefore seems likely that the defect underlying these human diseases also causes reduced embryonic viability in the rge chicken, making it a powerful model for studying the pathology involved in these associations. Furthermore, GNB3 is ubiquitously expressed, and the c.825C→T GNB3 splicing variant (MIM 139130) has been associated with hypertension, obesity, diabetes, low birth weight, coronary heart disease, and stroke in the human population. These findings implicate the β-subunit of cone transducin as the defective protein underlying the rge phenotype. Furthermore, a 70% reduction was found in immunoreactivity to anti-GNB3 in the rge-affected retina.Ĭonclusions. In silico modeling suggested that this mutation destabilized the protein. This mutation deleted a highly conserved aspartic acid residue in the third of seven WD domains in GNB3. The rge locus was refined and the gene for guanine nucleotide–binding protein β-3 ( GNB3), which encodes a cone transducin β subunit, was found to have a 3-bp deletion (D153del) that segregated with the rge phenotype. Linkage analysis, with previously uncharacterized microsatellite markers from chicken chromosome 1, was performed on 138 progeny of an rge/+ and an rge/rge cross, and candidate genes were sequenced. To identify the gene defect that causes blindness and the predisposition to embryonic death in the retinopathy globe enlarged (rge) chicken.
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