HSALR Mice Exhibit Co-Expression of Proteostasis Genes Prior to Development of Muscle Weakness Article Swipe
D Lazić
,
Vladimir Jovanović
,
J Karanović
,
Dušanka Savić‐Pavićević
,
Bogdan Jovanovic
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/ijms262110793
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/ijms262110793
Myotonic dystrophy type 1 (DM1) is a progressive multisystemic disease caused by a CTG repeat expansion in the DMPK gene. The toxic mutant mRNA sequesters MBNL proteins, disrupting global RNA metabolism. Although alternative splicing in DM1 skeletal muscle pathology has been extensively studied, early-stage transcriptomic changes remained uncharacterized. To gain deeper and contextual insight into DM1 transcriptome, we performed the first Weighted Gene Co-expression Network Analysis (WGCNA) on skeletal muscle RNA sequencing data from the widely used DM1 mouse model HSALR (~250 CTG repeats). We identified 532 core genes using data from 16-week-old mice, an age before the onset of muscle weakness. Additional differential expression analysis across multiple HSALR datasets revealed 42 common up-regulated coding and non-coding genes. Within identified core genes, the pathway gene-pair signature analysis enabled contextual selection of functionally related genes involved in maintaining proteostasis, including endoplasmic reticulum (ER) protein processing, the ubiquitin-proteasome system (UPS), macroautophagy and mitophagy, and muscle contraction. The enrichment of ER protein processing with prevailing core genes related to ER-associated degradation suggests adaptive chaperone and UPS activation, while core genes such as Ambra1, Mfn2, and Usp30 indicate adaptations in mitochondrial quality control. Coordinated early alterations in processes maintaining protein homeostasis, critical for muscle mass and function, possibly reflect a response to cellular stress due to repeat expansion and appears before muscle weakness development. Although the study relies exclusively on transcriptomic analyses, it offers a comprehensive, hypothesis-generating perspective that pinpoints candidate pathways, preceding muscle weakness, for future mechanistic validation.
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- Landing Page
- https://doi.org/10.3390/ijms262110793
- https://www.mdpi.com/1422-0067/26/21/10793/pdf?version=1762426019
- OA Status
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- References
- 70
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https://openalex.org/W4415967022Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/ijms262110793Digital Object Identifier
- Title
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HSALR Mice Exhibit Co-Expression of Proteostasis Genes Prior to Development of Muscle WeaknessWork title
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
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2025-11-06Full publication date if available
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D Lazić, Vladimir Jovanović, J Karanović, Dušanka Savić‐Pavićević, Bogdan JovanovicList of authors in order
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https://doi.org/10.3390/ijms262110793Publisher landing page
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https://www.mdpi.com/1422-0067/26/21/10793/pdf?version=1762426019Direct link to full text PDF
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goldOpen access status per OpenAlex
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0Total citation count in OpenAlex
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