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Caratterizzazione fenotipica e funzionale di un topo knock-out condizionale einducibile per il canale pacemaker HCN4 : dottorato di ricerca in fisiologia : tesi di dottorato

Mandelli, Giacomo <1979- >

Tesi o dissertazioni - 2008

Functional and molecular characterisation of an HCN4 knock-out mouse Mandelli G., Viscomi C., Micheloni S., Baruscotti M. & DiFrancesco D. Tutor: Prof. Dario DiFrancesco Dept. of Biomolecular Sciences and Biotechnologies, University of Studies of Milan, Via Celoria 26 The cardiac If pacemaker current is typically expressed in the sinoatrial node where it underlies the diastolic “pacemaker” depolarization. Previous experiments on cardiac HCN4 KO mice suggest that HCN4 channels, the molecular correlates of the native If, are necessary to support life during embryonic development but not in the adult animal. To further investigate the role of HCN4 channels, we have generated a mouse line in which the HCN4 gene can be eliminated in a conditional and inducible manner, based on the Cre/loxP approach induced by tamoxifen injection. We found that induction of HCN4 KO is lethal. Of the 15 animals treated, all died within 3-8 days after tamoxifen administration; all of the 17 control animals undergoing the same treatment survived [...]
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