Fast-twitch skeletal muscle fiber adaptation to SERCA1 deficiency in a Dutch Improved Red and White calf pseudomyotonia case

• Missense mutations in ATP2A1 gene, encoding SERCA1 protein, cause pseudomyotonia.
• We studied pseudomyotonia in a Dutch Improved Red and White cross-breed calf.
• We provide evidence for selective deficiency of mutated SERCA1, but not of mRNA.
• The reduction of the expression of SERCA1 is not compensated by the SERCA2 isoform.
• Pathological fibers are characterized by a broad distribution of mitochondria.

Missense mutations in ATP2A1 gene, encoding SERCA1 protein, cause a muscle disorder designed as congenital pseudomyotonia (PMT) in Chianina and Romagnola cattle or congenital muscular dystonia1 (CMD1) in Belgian Blue cattle. Although PMT is not life-threatening, CMD1 affected calves usually die within a few weeks of age as a result of respiratory complication. We have recently described a muscular disorder in a double muscle Dutch Improved Red and White cross-breed calf. Mutation analysis revealed an ATP2A1 mutation identical to that described in CMD1, even though clinical phenotype was quite similar to that of PMT. Here, we provide evidence for a deficiency of mutated SERCA1 in PMT affected muscles of Dutch Improved Red and White calf, but not of its mRNA. The reduced expression of SERCA1 is selective and not compensated by the SERCA2 isoform. By contrast, pathological muscles are characterized by a broad distribution of mitochondrial markers in all fiber types, not related to intrinsic features of double muscle phenotype and by an increased expression of sarcolemmal calcium extrusion pump. Calcium removal mechanisms, operating in muscle fibers as compensatory response aimed at lowering excessive cytoplasmic calcium concentration caused by SERCA1 deficiency, could explain the difference in severity of clinical signs.