Induction of R201C Mutant Gαs Modifies Mutant Kras-driven Murine Pancreatic Tumorigenesis and Leads to Differentiated Ductal Phenotypes

The human GNAS gene is imprinted in a tissue-specific manner, being expressed primarily from the maternal allele in pituitary, thyroid, renal proximal tubules, and gonads, but is supposed to be biallelically expressed with an equal allelic expression in most other tissues. We analysed allelic expression of Gαs using Pyrosequencing. By genotyping the GNAS T393C polymorphism we quantified mRNA transcripts in lymphoblasts (Ly, n = 11), peripheral blood mononuclear cells (PBMC, n = 18), mammary adipose tissue (MAT, n = 23) and heart tissue (HT, n = 44). Allelic expression analysis revealed an unequal allelic expression (ratio maternal/total × 100 ± SEM: 55.7 ± 1% (95% CI 53.4–58.1%) in Ly, 56.1 ± 0.8 (95% CI 54.5–57.7%) in PBMC, 54.5 ± 0.8% (95% CI 53–56.1%) in MAT and 54.1 ± 0.6% (95% CI 53–55.3%) in HT). Maternal ratio differed significantly from the mean (p < 0.0001). This phenomenon may be a general feature existing in all tissues.