Objective—To determine whether there was genetic linkage between the recurrent exertional rhabdomyolysis (RER) trait in Thoroughbred horse pedigrees and DNA markers in genes (the sarcoplasmic reticulum calcium release channel [RYR1] gene, the sarcoplasmic reticulum calcium ATPase [ATP2A1] gene, and the transverse tubule dihydropyridine receptor-voltage sensor [CACNA1S] gene) that are important in myoplasmic calcium regulation.
Animals—34 horses in the University of Minnesota RER resource herd and 62 Thoroughbreds from 3 families of Thoroughbreds outside of the university in which RER-affected status was assigned after 2 or more episodes of ER had been observed.
Procedures—Microsatellite DNA markers from the RYR1, ATP2A1, and CACNA1S gene loci on equine chromosomes 10, 13, and 30 were identified. Genotypes were obtained for all horses in the 4 families affected by RER, and data were used to test for linkage of these 3 loci to the RER phenotype.
Results—Analysis of the RYR1, CACNA1S, and ATP2A1 microsatellites excluded a link between those markers and the RER trait.
Conclusions and Clinical Relevance—It is likely that the heritable alterations in muscle contractility that are characteristic of RER are caused by a gene that is not yet known to cause related muscle disease in other species.
Objective—To evaluate whether biochemical or genetic alterations in AMP-activated protein kinase (AMPK) play a role in the development of polysaccharide storage myopathy (PSSM) in Quarter Horses.
Animals—30 PSSM-affected and 30 unaffected (control) Quarter Horses.
Procedures—By use of an established peptide phosphotransfer assay, basal and maximal AMPK activities were measured in muscle biopsy samples obtained from 6 PSSM-affected and 6 control horses. In 24 PSSM-affected and 24 control horses, microsatellite markers identified from the chromosomal locations of all 7 AMPK subunit genes were genotyped with a fluorescent DNA fragment analyzer. Alleles of 2 of the AMPK γ subunit genes were genotyped via DNA sequencing. Allele frequencies of DNA markers in or near the AMPK subunit genes were measured in isolated genomic DNA.
Results—No differences in basal or maximal muscle AMPK enzyme activities between PSSM-affected and control horses were detected. There were also no differences in allele frequencies for microsatellite markers near any of the 7 AMPK subunit genes between the 2 groups. Furthermore, previously known and newly identified alleles of 2 equine AMPK γ subunit genes were also not associated with PSSM.
Conclusions and Clinical Relevance—These results have provided no evidence to indicate that AMPK plays a causative role in PSSM in American Quarter Horses.
Objective—To develop a diagnostic test for recurrent
exertional rhabdomyolysis (RER) in Thoroughbreds that
relied on in vitro contracture of muscle biopsy specimens
and determine whether the inheritance pattern
of RER diagnosed on the basis of this contracture test
was consistent with an autosomal dominant trait.
Animals—8 adult horses with RER and 16 control
adult horses for development of the contracture test;
23 foals for inheritance of RER.
Procedure—External intercostal muscle biopsy specimens
from the 24 adult horses were tested for contracture
in response to halothane and caffeine, and
criteria for a positive test result were determined.
These criteria were then applied to results for the 23
foals to determine whether they had RER. Simple
segregation analysis was performed to determine
whether results were consistent with a dominant pattern
Results—Results of the contracture test were positive
for 5 of the 12 colts and 4 of the 11 fillies. Results
of segregation analysis were consistent with an autosomal
dominant pattern of inheritance. Two sires with
RER produced colts with RER, supporting the hypothesis
that RER had an autosomal, rather than an
X-linked, inheritance pattern. In addition, in 1
instance, an unaffected colt was produced by 2 affected
parents, which was not consistent with a recessive
mode of inheritance.
Conclusions and Clinical Relevance—Although the
expression of the RER trait is influenced by sex, temperament,
and diet, among other factors, results from
the in vitro muscle contracture test and this breeding
trial suggest that RER in Thoroughbreds can be modeled
as a genetic trait with an autosomal dominant pattern of
inheritance. ( J Am Vet Med Assoc 2005;227:762–767)