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 journalArticle

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 Ca2+ 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)
JournalJournal of Veterinary Internal Medicine
DOIs
StatePublished - Jan 1 2019

Fingerprint

Sarcoplasmic Reticulum Calcium-Transporting ATPases
rhabdomyolysis
Rhabdomyolysis
sarcoplasmic reticulum
Ca2-transporting ATPase
Regulator Genes
regulator genes
peptides
Calcium
calcium
Peptides
Horses
horses
Open Reading Frames
open reading frames
Amino Acid Sequence
amino acid sequences
Calsequestrin
Muscles
muscles

Keywords

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

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Coding sequences of sarcoplasmic reticulum calcium ATPase regulatory peptides and expression of calcium regulatory genes in recurrent exertional rhabdomyolysis. / Valberg, Stephanie J.; Soave, Kaitlin; Williams, Zoë J.; Perumbakkam, Sudeep; Schott, Melissa; Finno, Carrie J; Petersen, Jessica L.; Fenger, Clara; Autry, Joseph M.; Thomas, David D.

In: Journal of Veterinary Internal Medicine, 01.01.2019.

Research output: Contribution to journalArticle

Valberg, Stephanie J. ; Soave, Kaitlin ; Williams, Zoë J. ; Perumbakkam, Sudeep ; Schott, Melissa ; Finno, Carrie J ; Petersen, Jessica L. ; Fenger, Clara ; Autry, Joseph M. ; Thomas, David D. / Coding sequences of sarcoplasmic reticulum calcium ATPase regulatory peptides and expression of calcium regulatory genes in recurrent exertional rhabdomyolysis. In: Journal of Veterinary Internal Medicine. 2019.
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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 Ca2+ 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.",
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author = "Valberg, {Stephanie J.} and Kaitlin Soave and Williams, {Zo{\"e} J.} and Sudeep Perumbakkam and Melissa Schott and Finno, {Carrie J} and Petersen, {Jessica L.} and Clara Fenger and Autry, {Joseph M.} and Thomas, {David D.}",
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T1 - Coding sequences of sarcoplasmic reticulum calcium ATPase regulatory peptides and expression of calcium regulatory genes in recurrent exertional rhabdomyolysis

AU - Valberg, Stephanie J.

AU - Soave, Kaitlin

AU - Williams, Zoë J.

AU - Perumbakkam, Sudeep

AU - Schott, Melissa

AU - Finno, Carrie J

AU - Petersen, Jessica L.

AU - Fenger, Clara

AU - Autry, Joseph M.

AU - Thomas, David D.

PY - 2019/1/1

Y1 - 2019/1/1

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AB - 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 Ca2+ 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.

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KW - RYR1

KW - skeletal muscle

KW - tying up

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