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

Stephanie J. Valberg, Kaitlin Soave, Zoë J. Williams, Sudeep Perumbakkam, Melissa Schott, Carrie J. Finno, Jessica L. Petersen, Clara Fenger, Joseph M. Autry, David D. Thomas

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)933-941
Number of pages9
JournalJournal of veterinary internal medicine
Volume33
Issue number2
DOIs
StatePublished - Mar 1 2019

Bibliographical note

Funding Information:
Foundation for the National Institutes of Health, Grant/Award Number: R01HL129814, R37AG26160; Grayson Jockey Club Research Foundation; DDT NIH, Grant/Award Number: R01 HL129814, R37 AG26160; Morris Animal Foundation, Grant/Award Number: D16Eq004

Funding Information:
Funded by Morris Animal Foundation D16Eq004 and for DDT NIH grants R01 HL129814, R37 AG26160. The funding sources did not contribute to study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The assistance of Dr. James Slaughter, Dr. Susannah Lewis, referring veterinarians and Kentucky Equine Research is gratefully acknowledged.

Keywords

  • RYR1
  • exercise
  • myopathy
  • skeletal muscle
  • tying up

PubMed: MeSH publication types

  • Journal Article

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