Biochemical and genetic evaluation of the role of AMP-activated protein kinase in polysaccharide storage myopathy in Quarter Horses.
Abstract: 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. Methods: 30 PSSM-affected and 30 unaffected (control) Quarter Horses. Methods: 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 gamma 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 gamma subunit genes were also not associated with PSSM. Conclusions: These results have provided no evidence to indicate that AMPK plays a causative role in PSSM in American Quarter Horses.
Publication Date: 2007-10-06 PubMed ID: 17916014DOI: 10.2460/ajvr.68.10.1079Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research is centered on assessing if alterations at a biochemical or genetic level in the AMP-activated protein kinase (AMPK) contribute to the development of polysaccharide storage myopathy (PSSM) in Quarter Horses. The results of the study reveal no evidence to suggest that AMPK plays a causative role in PSSM among the horses studied.
Methods Employed in the Study
The researchers utilized several methods to evaluate the role of AMPK in PSSM:
- In order to measure both basal and maximal AMP-activated protein kinase activities, an established peptide phosphotransfer assay was used on muscle biopsy samples taken from 6 PSSM-affected horses and 6 control horses.
- In 24 PSSM-affected and 24 control horses, the researchers used genotyping with a fluorescent DNA fragment analyzer after identifying microsatellite markers from the chromosomal locations of all 7 AMPK subunit genes.
- Alleles of two AMPK gamma subunit genes were genotyped through DNA sequencing.
- DNA marker allele frequencies that were in or near the AMPK subunit genes were measured using isolated genomic DNA.
Findings of the Study
The findings highly suggest that AMPK does not contribute to the causation of PSSM in Quarter Horses:
- No differences were detected in basal or maximal muscle AMP-activated protein kinase enzyme activities between PSSM-affected and control horses.
- Similarly, there were no differences in allele frequencies for the microsatellite markers found near any of the AMPK subunit genes between the PSSM-affected and control horses.
- Additionally, both previously known and newly identified alleles of the two equine AMP-activated protein kinase gamma subunit genes showed no association with PSSM.
Conclusions of the Study
Given the results of their research, the study concludes that:
- There isn’t sufficient evidence to suggest that the AMP-activated protein kinase has a causative role in the development of polysaccharide storage myopathy in the Quarter Horses studied.
Cite This Article
APA
Dranchak PK, Leiper FC, Valberg SJ, Piercy RJ, Carling D, McCue ME, Mickelson JR.
(2007).
Biochemical and genetic evaluation of the role of AMP-activated protein kinase in polysaccharide storage myopathy in Quarter Horses.
Am J Vet Res, 68(10), 1079-1084.
https://doi.org/10.2460/ajvr.68.10.1079 Publication
Researcher Affiliations
- Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108, USA.
MeSH Terms
- AMP-Activated Protein Kinases
- Animals
- Calcium-Calmodulin-Dependent Protein Kinase Kinase / genetics
- Calcium-Calmodulin-Dependent Protein Kinase Kinase / metabolism
- Codon / genetics
- Glycogen Storage Disease / enzymology
- Glycogen Storage Disease / genetics
- Glycogen Storage Disease / veterinary
- Horse Diseases / enzymology
- Horse Diseases / genetics
- Horses
- Microsatellite Repeats
- Multienzyme Complexes / genetics
- Multienzyme Complexes / metabolism
- Muscle, Skeletal / enzymology
- Polysaccharides / metabolism
- Protein Serine-Threonine Kinases / genetics
- Protein Serine-Threonine Kinases / metabolism
- Rats
- Reference Values
- Species Specificity
Grant Funding
- MC_U120027537 / Medical Research Council
Citations
This article has been cited 4 times.- Naylor RJ, Livesey L, Schumacher J, Henke N, Massey C, Brock KV, Fernandez-Fuente M, Piercy RJ. Allele copy number and underlying pathology are associated with subclinical severity in equine type 1 polysaccharide storage myopathy (PSSM1). PLoS One 2012;7(7):e42317.
- Barrey E, Mucher E, Jeansoule N, Larcher T, Guigand L, Herszberg B, Chaffaux S, Guérin G, Mata X, Benech P, Canale M, Alibert O, Maltere P, Gidrol X. Gene expression profiling in equine polysaccharide storage myopathy revealed inflammation, glycogenesis inhibition, hypoxia and mitochondrial dysfunctions. BMC Vet Res 2009 Aug 7;5:29.
- McCue ME, Valberg SJ, Miller MB, Wade C, DiMauro S, Akman HO, Mickelson JR. Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis. Genomics 2008 May;91(5):458-66.
- Chowdhary BP, Raudsepp T. The horse genome derby: racing from map to whole genome sequence. Chromosome Res 2008;16(1):109-27.
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