Transgenic mouse model for myotonic dystrophy: dmsxl carrying >1000 ctg repeats

This transgenic mice model contains large human genomic DNA sequence carrying the DMPK gene with very large repeat (>1200 CTG). They show intergenerational and somatic instability biased towards expansions. Homozygous mice, expressing enough toxic RNA carrying CUG expansion display a clear phenotype and some DM1 features: Growth retardation, muscle weakness, myotonia, splicing defects in muscle heart and brain, especially at young ages. Brain, muscles and heart abnormalities are under characterisation.

Interest / Relevance: These mice are used to study the molecular and patho-physiological consequences of CTG expansions. They are also used for gene therapy experiments and pharmacological preclinical studies. Because the DMPK transgene is expressed under the control of its own promoter and in various tissues (as in human), they can be used for systemic preclinical experiments.

Keywords: mice model, myotonic dystrophy type 1, DM1

Publications:

Calcium handling abnormalities increase arrhythmia susceptibility in DMSXL myotonic dystrophy type 1 mice.
Cupelli M, Ginjupalli VKM, Reisqs JB, Sleiman Y, El-Sherif N, Gourdon G, Puymirat J, Chahine M, Boutjdir M. Biomed Pharmacother. 2024 Oct 17;180:117562. doi: 10.1016/j.biopha.2024.117562. Online ahead of print.

Electrophysiological basis of cardiac arrhythmia in a mouse model of myotonic dystrophy type 1.
Ginjupalli VKM, Cupelli M, Reisqs JB, Sleiman Y, El-Sherif N, Gourdon G, Puymirat J, Chahine M, Boutjdir M. Front Physiol. 2023 Sep 21;14:1257682. doi: 10.3389/fphys.2023.1257682. eCollection 2023. PMID: 37811496

Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring.
Golini E, Rigamonti M, Raspa M, Scavizzi F, Falcone G, Gourdon G, Mandillo S. Front Behav Neurosci. 2023 Mar 2;17:1130055. doi: 10.3389/fnbeh.2023.1130055. eCollection 2023. PMID: 36935893

Myotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes.
Dincã DM, Lallemant L, González-Barriga A, Cresto N, Braz SO, Sicot G, Pillet LE, Polvèche H, Magneron P, Huguet-Lachon A, Benyamine H, Azotla-Vilchis CN, Agonizantes-Juárez LE, Tahraoui-Bories J, Martinat C, Hernández-Hernández O, Auboeuf D, Rouach N, Bourgeois CF, Gourdon G, Gomes-Pereira M. Nat Commun. 2022 Jul 4;13(1):3841. doi: 10.1038/s41467-022-31594-9. PMID: 35789154

Reference:

RT00399