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Title: The D153del mutation in GNB3 gene causes tissue specific signalling patterns and an abnormal renal morphology in rge chickens
Authors: Tummala, Hemanth
Fleming, Stewart
Hocking, Paul M.
Wehner, Daniel
Naseem, Zahid
Ali, Manir
Inglehearn, Christopher F.
Zhelev, Nikolai Z.
Lester, Douglas H.
Affiliation: University of Abertay Dundee. School of Contemporary Sciences
Keywords: Protein Beta-3 subunit
Heterotrimeric G-proteins
Splice variant
Retinal degeneration
Coupled receptors
Golgi membranes
825T Allele
Issue Date: Aug-2011
Publisher: Public Library of Science
Type: Journal Article
Refereed: peer-reviewed
Rights: This is the published version of this article. Reproduced by permission of the publisher. Published version (c)H. Tummala, S. Fleming, P.M. Hocking, D. Wehner, Z. Naseem, M. Ali, C.F. Inglehearn, N. Zhelev, D.H. Lester, available from http://dx.doi.org/10.1371/journal.pone.0021156
Citation: Tummala, H., et al. 2011. The D153del mutation in GNB3 gene causes tissue specific signalling patterns and an abnormal renal morphology in rge chickens. PLoS ONE. 6(8): e21156. Available from http://dx.doi.org/10.1371/journal.pone.0021156
Abstract: Background The GNB3 gene is expressed in cone but not rod photoreceptors of vertebrates, where it acts as the β transducin subunit in the colour visual transduction process. A naturally occurring mutation ‘D153del’ in the GNB3 gene causes the recessively inherited blinding phenotype retinopathy globe enlarged (rge) disease in chickens. GNB3 is however also expressed in most other vertebrate tissues suggesting that the D153del mutation may exert pathological effects that outlie from eye. Principal Findings Recombinant studies in COS-7 cells that were transfected with normal and mutant recombinant GNB3 constructs and subjected to cycloheximide chase showed that the mutant GNB3d protein had a much shorter half life compared to normal GNB3. GNB3 codes for the Gβ3 protein subunit that, together with different Gγ and Gα subunits, activates and regulates phosphorylation cascades in different tissues. As expected, the relative levels of cGMP and cAMP secondary messengers and their activated kinases such as MAPK, AKT and GRK2 were also found to be altered significantly in a tissue specific manner in rge chickens. Histochemical analysis on kidney tissue sections, from rge homozygous affected chickens, showed the chickens had enlargement of the glomerular capsule, causing glomerulomegaly and tubulointerstitial inflammation whereas other tissues (brain, heart, liver, pancreas) were unaffected. Significance These findings confirm that the D153del mutation in GNB3 gene targets GNB3 protein to early degradation. Lack of GNB3 signalling causes reduced phosphorylation activity of ERK2 and AKT leading to severe pathological phenotypes such as blindness and renal abnormalities in rge chickens.
URI: http://hdl.handle.net/10373/1098
ISSN: 1932-6203
Appears in Collections:Science Engineering & Technology Collection

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