![]() ![]() ![]() Nous avons validé et caractérisé deux lignées de souris knock-in (KI) exprimant le récepteur mutant d'internalisation P2X4mCherryIN dans les neurones excitateurs du cerveau antérieur (CamK2) ou dans toutes les cellules exprimant le récepteur P2X4 de façon native (CMV). Une question clé concernant le rôle de la signalisation purinergique dans la physiologie et la physiopathologie est la fonction de l'augmentation du nombre de récepteurs P2X4 en surface observée dans différents types cellulaires de manière spécifique.Pour élucider les fonctions cellulaires spécifiques du récepteur P2X4 dans un contexte pathologique, une lignée de souris transgéniques conditionnelle (P2X4mCherryIN floxée) a été créée permettant la substitution du motif d'internalisation de P2X4 par la protéine fluorescente mCherry, sous la dépendance de la Cre recombinase, empêchant ainsi l'endocytose constitutive du récepteur P2X4. Le récepteur P2X4 a une expression étendue dans le système nerveux central (SNC) au niveau des neurones et des cellules gliales ainsi que dans divers types cellulaires périphériques. La signalisation purinergique ainsi que l'augmentation en surface des récepteurs ionotropiques P2X4 activé par l'ATP sont exacerbés dans divers troubles du SNC dont la sclérose latérale amyotrophique (SLA).
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