ABSENCE OF TRPCS LEADS TO INCREASED BODY WEIGHT

KARINA FORMOSO; MARIA AGUSTINA VIDAL; SUSPERREGUY, SEBASTIAN; JULIETA MANSILLA RICARTTI; MARIA VICTORIA REVUELTA

Congreso; Reunion anual de la Sociedad Argentina de Investigación Clínica; 2019

TRPC genes encode non-selective Ca2+-permeable cation channels implicated in the mechanism of store operated Ca2+ entry. TRPC channels have been increasingly linked to a diverse number of pathologies. The mutation, down or up-regulation of any of these channels may lead to diseases that include cardiopathies, neuronal disorders and immune deficiencies among others. This highlights the potential of TRPC channels to become novel therapeutic targets and also provides evidence of their physiological function. The absence of specific inhibitors limits the study of these channels and lead to the development of knockout (KO) mice. KO of each and every one of the 7 TRPC genes, separately, has yielded mice with distinctive phenotypes, some favorable, others detrimental to the health of the mouse. It is important to note that TRPCs 1-7 have overlapping functions that could mask the effect of removing just one of these channels. HeptaKO mice are alive and breed descendants. Nonetheless, they present increased body weight 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 their WT counterparts. This analysis may allow us to determine a possible link between TRPCs and signalling pathways that could explain the observed phenotype(s). To this end we performed a pathway enrichment analysis from which we determined that one of the most prevalent modified pathway is circadian rhythm. Interestingly, the latter has been increasingly related to metabolic syndrome that is characterised by localised fat around the waist, elevated blood pressure, high triglycerides, elevated blood sugar, and low HDL cholesterol. These results could thus present the TRPCs as potential therapeutic targets for this syndrome.