ABSENCE OF TRPCS LEADS TO INCREASED BODY WEIGHT

KARINA FORMOSO; SEBASTIÁN SUSPERREGUY; MARIA VICTORIA REVUELTA; MARIA AGUSTINA VIDAL; JULIETA MANSILLA RICARTTI; LUTZ BIRNBAUMER

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Abstract/Resumen: TRPC genes encode non-selective Ca2+-permeable cation channels implicated in the mechanism of storeoperated Ca2+ entry. TRPC channels have been increasinglylinked to a diverse number of pathologies. The mutation, down orup-regulation of any of these channels may lead to diseases thatinclude cardiopathies, neuronal disorders and immunedeficiencies among others. This highlights the potential of TRPCchannels to become novel therapeutic targets and also providesevidence of their physiological function. The absence of specificinhibitors limits the study of these channels and led to thedevelopment of knockout (KO) mice. KO of each and every oneof the 7 TRPC genes, separately, has yielded mice withdistinctive phenotypes, some favourable, others detrimental tothe health of the mouse. It is important to note that TRPCs 1-7have overlapping functions that could mask the effect ofremoving just one of these channels. HeptaKO mice are alive andbreed descendants. Nonetheless, they present increased bodyweight compared to WT mice. Our laboratory has obtained RNAseq data from eight tissues (liver, heart, spleen, testis, lung,kidney, midbrain and forebrain) of the heptaKO mice and theirWT counterparts. This analysis may allow us to determine apossible link between TRPCs and signalling pathways that couldexplain the observed phenotype(s). To this end we performed apathway enrichment analysis from which we determined that oneof the most prevalent modified pathways is circadian rhythm.Interestingly, the latter has been increasingly related tometabolic syndrome that is characterised by localised fat aroundthe waist, elevated blood pressure, high triglycerides, elevatedblood sugar, and low HDL cholesterol. These results could thuspresent the TRPCs as potential therapeutic targets for thissyndrome