Congenital Pseudomyotonia (PMT) is an inherited muscular disease affecting bovine species. Clinically it is characterized by an exercise-induced muscle contraction. The aetiology is related to a prolonged high level of cytosolic free Ca2+ ion in muscle fibers. Genetic analysis has provided evidence of mutations in ATP2A1 gene coding for Sarco(endo)plasmic Reticulum Ca2+-ATPase, isoform1 (SERCA1) a membrane protein involved in re-uptake of calcium from cytosol into sarcoplasmic reticulum [1]. The clinical symptoms and genetic correlations make bovine PMT the true counterpart of human Brody’s disease [2,3,4]. SERCA1 has been largely investigated in structure, domains and functional mechanisms [5,6]. Mutant cDNAs were expressed in cell culture and SERCA1-null mice has been created to investigate the importance of this protein and the implication of the different domains. It has been demonstrated how a single substitution of Arginine 560 (in mouse and rabbit) in domain N leads to a severe alteration of the protein conformation with a substantial reduction of its functionality [7,8]. Our group is working on PMT and interestingly a pathological case, a Dutch cross-breed calf, has shown a natural mutation in ATP2A1 gene leading to a substitution of Arginine 559, corresponding to Arginine 560 in mouse and rabbit. This spontaneous mutation produce a situation similar to the experimental one. Some preliminary histological and biochemical results have been published in a case report [9]. Here we present new histological analysis and early results in the study of the bovine natural mutation in heterologous system.

Natural mutation in bovine Sarco(endo)plasmatic Reticulum Ca2+ATPase1 (SERCA1): histological and biochemical aspect in the muscle fibers

DOROTEA, TIZIANO;MASCARELLO, FRANCESCO;SACCHETTO, ROBERTA
2013

Abstract

Congenital Pseudomyotonia (PMT) is an inherited muscular disease affecting bovine species. Clinically it is characterized by an exercise-induced muscle contraction. The aetiology is related to a prolonged high level of cytosolic free Ca2+ ion in muscle fibers. Genetic analysis has provided evidence of mutations in ATP2A1 gene coding for Sarco(endo)plasmic Reticulum Ca2+-ATPase, isoform1 (SERCA1) a membrane protein involved in re-uptake of calcium from cytosol into sarcoplasmic reticulum [1]. The clinical symptoms and genetic correlations make bovine PMT the true counterpart of human Brody’s disease [2,3,4]. SERCA1 has been largely investigated in structure, domains and functional mechanisms [5,6]. Mutant cDNAs were expressed in cell culture and SERCA1-null mice has been created to investigate the importance of this protein and the implication of the different domains. It has been demonstrated how a single substitution of Arginine 560 (in mouse and rabbit) in domain N leads to a severe alteration of the protein conformation with a substantial reduction of its functionality [7,8]. Our group is working on PMT and interestingly a pathological case, a Dutch cross-breed calf, has shown a natural mutation in ATP2A1 gene leading to a substitution of Arginine 559, corresponding to Arginine 560 in mouse and rabbit. This spontaneous mutation produce a situation similar to the experimental one. Some preliminary histological and biochemical results have been published in a case report [9]. Here we present new histological analysis and early results in the study of the bovine natural mutation in heterologous system.
ItPA 8th Annual National Conference Abstract Volume
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/2695880
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact