Myofibrillar Myopathy in Horses

Myofibrillar myopathy (MM) is a muscle disease that effects mainly Arabians and Warmbloods. Arabians usually display intermittent tying up while Warmbloods display decreasing performance in middle age warmbloods. Previously a lot of these horses were identified as polysaccharide storage myopathy (PSSM) but recent work identifies this as a different disease with similar symptoms and even some overlapping pathology. One difference may give you a clue you have MM and that is muscle enzymes are not as elevated as in horses with other forms of tying up. In Warmbloods there may not even be elevation of muscle enzymes so can appear as any other cause of poor performance. To diagnose this disease requires special staining of muscle biopsy and is currently being done at the University of Michigan School of Veterinary Medicine. You should contact them for specifics on biopsy submission. For more see https://cvm.msu.edu/research/faculty-research/comparative-medical-genetics/valberg-laboratory/myofibrillar-myopathy
DrO

Integrated proteomic and transcriptomic profiling identifies aberrant gene and protein expression in the sarcomere, mitochondrial complex I, and the extracellular matrix in Warmblood horses with myofibrillar myopathy
BMC Genomics. 2021 Jun 11;22(1):438.
Authors
Zoë J Williams 1 , Deborah Velez-Irizarry 2 , Keri Gardner 2 , Stephanie J Valberg 2
Affiliations

1 Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI, 48824, USA. will3084@msu.edu.
2 Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI, 48824, USA.

PMID: 34112090
DOI: 10.1186/s12864-021-07758-0

Abstract

Background: Myofibrillar myopathy in humans causes protein aggregation, degeneration, and weakness of skeletal muscle. In horses, myofibrillar myopathy is a late-onset disease of unknown origin characterized by poor performance, atrophy, myofibrillar disarray, and desmin aggregation in skeletal muscle. This study evaluated molecular and ultrastructural signatures of myofibrillar myopathy in Warmblood horses through gluteal muscle tandem-mass-tag quantitative proteomics (5 affected, 4 control), mRNA-sequencing (8 affected, 8 control), amalgamated gene ontology analyses, and immunofluorescent and electron microscopy.

Results: We identified 93/1533 proteins and 47/27,690 genes that were significantly differentially expressed. The top significantly differentially expressed protein CSRP3 and three other differentially expressed proteins, including, PDLIM3, SYNPO2, and SYNPOL2, are integrally involved in Z-disc signaling, gene transcription and subsequently sarcomere integrity. Through immunofluorescent staining, both desmin aggregates and CSRP3 were localized to type 2A fibers. The highest differentially expressed gene CHAC1, whose protein product degrades glutathione, is associated with oxidative stress and apoptosis. Amalgamated transcriptomic and proteomic gene ontology analyses identified 3 enriched cellular locations; the sarcomere (Z-disc & I-band), mitochondrial complex I and the extracellular matrix which corresponded to ultrastructural Z-disc disruption and mitochondrial cristae alterations found with electron microscopy.

Conclusions: A combined proteomic and transcriptomic analysis highlighted three enriched cellular locations that correspond with MFM ultrastructural pathology in Warmblood horses. Aberrant Z-disc mechano-signaling, impaired Z-disc stability, decreased mitochondrial complex I expression, and a pro-oxidative cellular environment are hypothesized to contribute to the development of myofibrillar myopathy in Warmblood horses. These molecular signatures may provide further insight into diagnostic biomarkers, treatments, and the underlying pathophysiology of MFM.

Keywords: Gluteal muscle; Myofibrillar myopathy; Proteomics; Transcriptomics; Warmblood; Z-disc.