title: Post-natal heart adaptation in a knock-in mouse model of calsequestrin 2-linked recessive catecholaminergic polymorphic ventricular tachycardia.
abstract: Cardiac calsequestrin (CASQ2) contributes to intracellular Ca(2+) homeostasis by virtue of its low-affinity/high-capacity Ca(2+) binding properties, maintains sarcoplasmic reticulum (SR) architecture and regulates excitation-contraction coupling, especially or exclusively upon β-adrenergic stimulation. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease associated with cardiac arrest in children or young adults. Recessive CPVT variants are due to mutations in the CASQ2 gene. Molecular and ultra-structural properties were studied in hearts of CASQ2(R33Q/R33Q) and of CASQ2(-/-) mice from post-natal day 2 to week 8. The drastic reduction of CASQ2-R33Q is an early developmental event and is accompanied by down-regulation of triadin and junctin, and morphological changes of jSR and of SR-transverse-tubule junctions. Although endoplasmic reticulum stress is activated, no signs of either apoptosis or autophagy are detected. The other model of recessive CPVT, the CASQ2(-/-) mouse, does not display the same adaptive pattern. Expression of CASQ2-R33Q influences molecular and ultra-structural heart development; post-natal, adaptive changes appear capable of ensuring until adulthood a new pathophysiological equilibrium.
authors.affiliation: Dipartimento di Scienze Biomediche dell'Università di Padova, Istituto di Neuroscienze del CNR, Istituto Interuniversitario di Miologia, viale G. Colombo 3, 35121 Padova, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Valle
authors.affiliation: Dipartimento di Neuroscienze e Imaging dell'Università Gabriele D'Annunzio, Centro Scienze dell'Invecchiamento, Chieti, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Boncompagni
authors.affiliation: Dipartimento di Biomedicina Comparata ed Alimentazione dell'Università di Padova, Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Sacchetto
authors.affiliation: Dipartimento di Neuroscienze e Imaging dell'Università Gabriele D'Annunzio, Centro Scienze dell'Invecchiamento, Chieti, Italy.
authors.forename: Feliciano
authors.initials: F
authors.lastname: Protasi
authors.affiliation: Dipartimento di Scienze Biomediche dell'Università di Padova, Istituto di Neuroscienze del CNR, Istituto Interuniversitario di Miologia, viale G. Colombo 3, 35121 Padova, Italy. Electronic address: pompeo.volpe@unipd.it.
authors.forename: Pompeo
authors.initials: P
authors.lastname: Volpe
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D002155:Calsequestrin / Q000235:genetics*; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D005808:Genes, Recessive; D006321:Heart / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020125:Mutation, Missense / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000235:genetics* / Q000503:physiopathology*; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D002155:Calsequestrin; C514388:casq2 protein, mouse
keywords: CASQ2 knock-out; CASQ2 mutation; Catecholaminergic polymorphic ventricular tachycardia; ER stress