Abstract

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.

Original languageEnglish
Pages (from-to)888-97
Number of pages10
JournalNeuromuscular Disorders
Volume25
Issue number11
DOIs
Publication statusPublished - Nov 2015
Externally publishedYes

Keywords

  • Adaptation, Physiological/physiology
  • Animals
  • Cattle
  • HEK293 Cells
  • Humans
  • Isaacs Syndrome/pathology
  • Isoenzymes/metabolism
  • Mitochondria/metabolism
  • Muscle Fibers, Fast-Twitch/pathology
  • Mutation, Missense
  • RNA, Messenger/metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases/deficiency

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