PMC

Mean GS activity in the presence and absence of its allosteric activator, glucose 6-phosphate (G6P).
* indicates significant difference between PSSM and controls

Minimally conserved haplotype in all breeds is highlighted and the length in Kb in different breeds indicated on the right. The Kb on the horizontal position is the relative position of each SNP within the 2 Mb contig containing the GYS1 gene. The GYS1 A allele producing the Arg309His GS mutation is indicated at the 819 Kb position as the PSSMSNPEXON6 SNP.

Multiple amino acid alignment of glycogen synthase 1 (skeletal muscle isoform) and glycogen synthase 2 (liver isoform). Residue 309 at the site of the GYS1 PSSM mutation, and the surrounding amino acids, are highly conserved across species and across both GS isoforms.

Panel a: A Quarter horse on left (60” tall at height of shoulder) and a Belgian Draft horse (72” tall at height of shoulder) both with PSSM. Panel b: A Quarter Horse with typical signs of muscle cramping accompanying an episode of exertional rhabdomyolysis. Panel c: A Quarter Horse severely afflicted with exertional rhabdomyolysis that can only stand for a few minutes with assistance from a sling.

Map of ECA10p and p values association of MS marker alleles with PSSM in the initial and follow-up case and control cohorts. From left to right: idiogram of ECA10p with FISH-anchored loci (21); Radiation hybrid map of ECA10p with comparatively mapped loci to HSA19 (21); p values for chi-squared comparison of MS allele frequencies in the initial population and the follow-up population. The GYS1 gene at the 54.1 Mb position on HSA19 is indicated.

Panel a: Periodic acid Schiff’s (PAS) staining of cross-section of semitendinosus muscle from a normal horse demonstrating the presence of normal glycogen. Panel b: PAS staining of the same muscle from a horse with PSSM showing crystalline PAS positive inclusions of abnormal polysaccharide in multiple fibers. Panel c: Amylase digestion and PAS staining of a serial section of muscle from the PSSM horse in Panel b. Normal glycogen has been digested, whereas the abnormal polysaccharide is amylase-resistant.