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\u2019s 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
