Characterization of a mouse model for Tubular Aggregate Myopathy and development of small molecules

Tubular aggregate myopathy (TAM) is one of a cluster of rare genetic diseases, together with Stormorken syndrome and York platelet syndrome (YPS). The aetiology of these diseases is the mutation in one of two key proteins, ORAIi and STIMÍ. Both proteins are the principai protagonists in Store-Operated Calcium Entry (SOC Entry), a mechanism of calcium homeostasis. Up to now, no mouse model has been designed bearing a luminal STIM1 mutation associated with the clinical diagnosis of any of the diseases. A mouse model bearing 11 15F mutation, which is associated with TAM and YPS, is extremely needed, to guarantee the effectiveness of putative treatment in patients bearing luminal STIM1 mutations. This thesis project demonstrates that the KI-STIM" mouse model is valid for both TAM and YPS, confirming at the same time the hypothesis of some authors, who defend that TAM, Stormorken, and YPS are indeed the spectra of the same disease whose symptoms differences are base in the position and effect of the point mutation.