Serum inflammatory cytokines as disease biomarkers in the DE50-MD dog model of Duchenne muscular dystrophy

Piercy, Richard; Riddell, Dominique; Hildyard, John; Harron, Rachel; Wells, Dominic

Abstract

Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease, caused by mutations in the dystrophin gene, characterised by cycles of muscle degeneration, inflammation and regeneration. The DE50-MD dog is a canine model of DMD that closely mimics the human DMD phenotype. We quantified a panel of proteins associated with inflammation in the serum of DE50-MD dogs in order to identify biomarkers for future pre-clinical trials. Serum protein concentrations were quantified by Luminex assay in samples from wild-type (WT) and DE50-MD dogs aged between 3 and 18 months. Significantly higher concentrations of C-C motif chemokine ligand 2 (CCL2), granulocyte-macrophage colony-stimulating factor, keratinocyte chemotactic-like, TNF-, and interleukins (IL)-2, IL6, IL7, IL8, IL10, IL15 and IL18, were detected in DE50-MD compared to WT serum. Of these, CCL2 best differentiated the 2 genotypes. Relative quantity of CCL2 mRNA was greater in DE50-MD vastus lateralis muscle than WT dogs and immunohistochemistry showed co-localisation of CCL2 with leucocyte marker CD18 in areas of muscle with signs of recent degeneration in DE50-MD samples. In conclusion, the serum cytokine profile suggests that inflammation is a feature of the DE50-MD phenotype. Quantification of serum CCL2 in particular is a useful non-invasive biomarker of DE50-MD pathology.

Citation

Piercy, R., Riddell, D., Hildyard, J., Harron, R., & Wells, D. (2022). Serum inflammatory cytokines as disease biomarkers in the DE50-MD dog model of Duchenne muscular dystrophy. Neuromuscular Disorders, https://doi.org/10.1242/dmm.049394

• Journal Article Type: Article
• Acceptance Date: Dec 7, 2022
• Publication Date: Dec 9, 2022
• Deposit Date: Jan 12, 2021
• Publicly Available Date: Mar 24, 2023
• Print ISSN: 0960-8966
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1242/dmm.049394