However, GANT61 citations Bullido et al. demonstrated a significant increase in both MAPK activity and cAMP levels in HEK-293 cells transfected with recombinant GNB3 825T plasmid constructs, compared to 825C constructs. These results were consistent with observed biochemical changes in the brains of patients with Alzheimer��s disease . Despite the interest provoked by studies AP24534 showing that the enhanced signalling of GNB3s causes an increase in the risk of developing brain disorders, hypertension and coronary heart disease in humans, a definitive understanding of the mechanisms underlying these pathologies has not yet been reached. GNB3 has previously been shown to bind both Gai and Gas subunits and, more recently, to interact with specific gamma subunits, which thereby activate different isoforms of the PLC pathway . Interestingly other transcripts have been identified in association with T allele, which give rise to stable protein structures such as GNB3s2 . GNB3s2 is found to be activating the mitogenactivated protein kinase cascade suggesting that it is a biologically active GNB variant, which may play a role in the manifestation of the complex phenotype associated with the 825T-allele. Contrastingly another novel splice variant of GNB3, termed Gbeta3v, which is generated by alternative splicing of parts from intron 9 as a novel exon 10 of the GNB3 gene is found to have no association with the 825T-allele. GNB3v protein form stable dimers with c subunits but tend not to be biologically active in activating signalling pathways such as PLCb2 . However, the lack of an appropriate mouse model or the availability of GNB3-genotyped fresh human tissue suitable for biochemical studies has hindered further progress on elucidating the tissue specific pathways affected by GNB3 or its variants. We previously reported a mutation in the GNB3 gene, which causes a recessive, progressive retinal dystrophy known as retinopathy globe enlarged in chickens . In rge affected chickens there is a variable degree of vision loss within 24 hours of hatching, with progressive deterioration in vision over the next few weeks, leading to complete blindness after 8 weeks. Unusually for hereditary retinopathies, this vision loss is not the result of photoreceptor loss. The rge chickens do however show a progressive and significant developmental disruption of both rod and cone photoreceptor synaptic terminals .