Mutation in the guanine nucleotide–binding protein ß-3 causes retinal degeneration and embryonic mortality in chickens

Hemanth Tummala, Manir Ali, Paul Getty, Paul M. Hocking, David W. Burt, Chris F. Inglehearn, Douglas H. Lester

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


PURPOSE. To identify the gene defect that causes blindness and the predisposition to embryonic death in the retinopathy globe enlarged (rge) chicken.

METHODS. 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.

RESULTS. 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. This mutation deleted a highly conserved aspartic acid residue in the third of seven WD domains in GNB3. In silico modeling suggested that this mutation destabilized the protein. Furthermore, a 70% reduction was found in immunoreactivity to anti-GNB3 in the rge-affected retina.

CONCLUSIONS. These findings implicate the β-subunit of cone transducin as the defective protein underlying the rge phenotype. 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. 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.
Original languageEnglish
Pages (from-to)4714-4718
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Issue number11
Publication statusPublished - Nov 2006


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