Recently, a muscular disorder defined as "congenital
pseudomyotonia" was described in Chianina cattle, one of the most important Italian cattle breeds for quality meat and leather. The clinical phenotype of this disease is characterized by an exercise-induced muscle
contracture that prevents animals from performing muscular activities. On the basis of clinical symptoms, Chianina
pseudomyotonia appeared related to human Brody's disease, a rare inherited disorder of skeletal muscle function that results from a
sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1) deficiency caused by a defect in the ATP2A1 gene that encodes SERCA1. SERCA1 is involved in transporting
calcium from the cytosol to the lumen of the sarcoplasmic reticulum. Recently, we identified the genetic defect underlying Chianina cattle
pseudomyotonia. A missense mutation in exon 6 of the ATP2A1 gene, leading to an R164H substitution in the SERCA1
protein, was found. In this study, we provide biochemical evidence for a selective deficiency in SERCA1
protein levels in sarcoplasmic reticulum membranes from affected muscles, although
mRNA levels are unaffected. The reduction of SERCA1 levels accounts for the reduced Ca(2+)-
ATPase activity without any significant change in Ca(2+)-dependency. The loss of SERCA1 is not compensated for by the expression of the SERCA2
isoform. We believe that Chianina cattle
pseudomyotonia might, therefore, be the true counterpart of human Brody's disease, and that bovine species might be used as a suitable animal model.