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Background  Sarcolipin ( SLN ), myoregulin ( MRLN ), and dwarf open reading frame ( DWORF ) are transmembrane regulators of the sarcoplasmic reticulum calcium transporting ATPase (SERCA) that we hypothesized played a role in recurrent exertional rhabdomyolysis (RER).    Objectives  Compare coding sequences of  SLN ,  MRLN ,  DWORF  across species and between RER and control horses. Compare expression of muscle Ca 2+  regulatory genes between RER and control horses.    Animals  Twenty Thoroughbreds (TB), 5 Standardbreds (STD), 6 Quarter Horses (QH) with RER and 39 breed‐matched controls.    Methods  Sanger sequencing of SERCA regulatory genes with comparison of amino acid (AA) sequences among control, RER horses, human, mouse, and rabbit reference genomes. In RER and control gluteal muscle, quantitative real‐time polymerase chain reaction of SERCA regulatory peptides, the calcium release channel ( RYR1 ), and its accessory proteins calsequestrin ( CASQ1 ), and calstabin ( FKBP1A ).    Results  The  SLN  gene was the highest expressed horse SERCA regulatory gene with a uniquely truncated AA sequence (29 versus 31) versus other species. Coding sequences of  SLN, MRLN , and  DWORF  were identical in RER and control horses. A sex‐by‐phenotype effect occurred with lower  CASQ1  expression in RER males versus control males ( P  < .001) and RER females ( P  = .05) and higher  FKBP1A  ( P  = .01) expression in RER males versus control males.    Conclusions and Clinical Importance  The  SLN  gene encodes a uniquely truncated peptide in the horse versus other species. Variants in the coding sequence of  SLN, MLRN , or  DWORF  were not associated with RER. Males with RER have differential gene expression that could reflect adaptations to stabilize RYR1.

journal of veterinary internal medicine

Coding sequences of sarcoplasmic reticulum calcium ATPase regulatory peptides and expression of calcium regulatory genes in recurrent exertional rhabdomyolysis