Discovery and characterisation of the novel, pathological GNB3 mutation (D153del/ Gβ3D), in the retinopathy globe enlarged (rge) chicken

  • Hemanth Tummala

Student thesis: Doctoral Thesis


The common human GNB3 825C>T variant, which is present in 50% of the world’s chromosomes, has previously been shown to predispose individuals to hypertension, cardiac and neural disorders. This variant causes the production of a stable and gain of function protein Gβ3S- This thesis describes the discovery of a novel D153del mutation that produces an unstable, loss of function, protein Gβ3D in the recessively inherited, retinopathy globe enlarged (rge) chickens. This thesis also demonstrates that the normal Gβdownstream phosphorylation signalling pathways are significantly altered in a tissue specific manner in rge chicken organs and in a human GNB3 825TT lymphoblast cell line. In rge tissues expressing Gβ3D protein, the cAMP induced GRK2 phosphorylation activity is significantly altered. Moreover MAPK1 (ERK2) phosphorylation is significantly decreased compared to normal tissues. In contrast human 825TT cell lines expressing the Gβ3S protein, showed enhanced cAMP induced GRK2 and MAPK (ERK1 and ERK2) phosphorylation activity. These results confirm previous findings of 825C>T Gβstudies, that Gβ3S is indeed a hyper-activating structural variant, in contrast to the D153del Gp3D is a classical recessively inherited non-functional mutation.
Date of AwardSep 2008
Original languageEnglish
SupervisorDouglas H. Lester (Supervisor)


  • G-protein
  • Genetic polymorphism
  • GTPase
  • Pharmacogenetics
  • Splice variant
  • Signal transduction
  • Neurological disorders
  • Hypertension,
  • Cardiac disease

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