CHANGES IN GENE EXPRESSION IN TISSUES OF A MOUSE LACKING EXPRESSION OF ALL 7 GENES EN- CODING TRPC CHANNELS (HEPTAKO). A PRELIMINARY ANALYSIS.

FORMOSO, KARINA; MARIA VISTORIA REVUELTA; SUSPERREGUY, SEBASTIAN; MARIA DE LA PAZ SARASOLA; LEANDRO CERCHIETTI; BIRNBAUMER, LUTZ

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

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 upregulation 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 that limits the study of these channels lead to the development of KO mice. Knock out (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. Combining, by breeding, the seven KO alleles has yielded a mouse strain we refer to as HeptaKO. Surprisingly, the mice are alive and breed spawning heptaKO descendants. To date no comprehensive analysis of this mouse has been done that could explain the effects observed in the simple KOs.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. Here we will describe the preliminary results obtained from the analysis of the samples that could explain the differential response to different diseases involving TRPC channels and also why the sevenfold mutant mice are alive and breed normally.