Table 1. Preclinical assessment of therapeutic strategies in DM1 mouse models.

Mouse modela	Therapeutic strategiesb	Quantifiable phenotypes in target tissues				Limitations	Refs
		Skeletal muscle	Heart	CNS	Others
HSALR	Elimination of toxic RNA, disruption of RNA–MBNL protein interactions, MBNL upregulation, restoration of missplicing	Myotonia, myopathy, foci accumulation, MBNL1 sequestration, missplicing events	Not applicable	Not applicable	Not applicable	No muscle weakness, normal CELF1 levels	[43]
EpA960	Elimination of toxic RNA, disruption of RNA–MBNL protein interactions, MBNL upregulation, CELF1 downregulation, PKC inactivation	Myotonia, motor function, muscle wasting, myopathy, foci accumulation, MBNL1 sequestration, missplicing events	Cardiac conduction defects, cardiomyopathy, foci accumulation, MBNL1 sequestration, missplicing events	Not reported	Not reported	Leakage of transgene expression in skeletal muscle, high mortality due to cardiac complications	[9,53,54]
DM300 and/or DMSXL	Elimination of toxic RNA, disruption of RNA–MBNL protein interactions, MBNL upregulation, restoration of missplicing, modification of triplet repeat dynamics	Myotonia, myopathy, foci accumulation, muscle strength, missplicing events	Foci accumulation, missplicing events	Foci accumulation, missplicing events, tauopathy	Foci accumulation, missplicing events	Mild splicing abnormalities, interindividual variability, time-consuming breeding strategies	[47,49,51, 98,99]
DMPK-GFP-(CTG)5	Elimination of toxic RNA, NKX2-5 downregulation	Myotonia, myopathy, missplicing events.	Cardiac conduction defects	Not reported	Not reported	No muscle weakness, no RNA foci, short repeat sequence, high mortality	[52]
Mbnl1Δ3/Δ3	MBNL upregulation or replacement	Myotonia, myopathy, missplicing events	Cardiomyopathy	Motivation and apathy deficits	Not reported	No muscle weakness, normal CELF1 levels	[59,61]
TRECUGBP1	CELF1 downregulation, restoration of missplicing	Motor function, myopathy, muscle weight, missplicing events	Cardiac conduction defects, cardiomyopathy	Not reported	Not reported	High mortality	[11,12]

^aDifferent mouse lines have different advantages and limitations in assessing the benefits and efficacy of new therapeutic schemes in specific tissues and organ systems.

^bPossible therapeutic approaches are presented for mouse models that replicate key events in the biochemical cascade of RNA toxicity and develop relevant DM1 phenotypes.