On the use of D2.B10-Dmd^mdx/J (D2.mdx) Versus C57BL/10ScSn-Dmd^mdx/J (mdx) Mouse Models for Preclinical Studies on Duchenne Muscular Dystrophy: A Cautionary Note from Members of the TREAT-NMD Advisory Committee on Therapeutics

Article type: Article Commentary

Authors: Aartsma-Rus, Annemieke^{a; *} | van Putten, Maaike^a | Mantuano, Paola^b | De Luca, Annamaria^b

Affiliations: [a] Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands | [b] Department of Pharmacy-Drug Sciences, Section of Pharmacology, University of Bari “Aldo Moro”, Bari, Italy

Correspondence: [*] Correspondence to: Annemieke Aartsma-Rus, LUMC Postzone S4-4, Albinusdreef 2, 2333 ZA Leiden, the Netherlands, Tel.: +31 71 5269436; E-mail: [email protected].

Abstract: The C57BL/10ScSn-Dmdmdx/J (mdx) mouse model has been used by researchers for decades as a model to study pathology of and develop therapies for Duchenne muscular dystrophy. However, the model is relatively mildly affected compared to the human situation. Recently, the D2.B10-Dmdmdx/J (D2.mdx) mouse model was suggested as a more severely affected and therefore better alternative. While the pathology of this model is indeed more pronounced early in life, it is not progressive, and increasing evidence suggest that it actually partially resolves with age. As such, caution is needed when using this model. However, as preclinical experts of the TREAT-NMD advisory committee for therapeutics (TACT), we frequently encounter study designs that underestimate this caveat. We here provide context for how to best use the two models for preclinical studies at the current stage of knowledge.

Keywords: Preclinical research, mouse models, pathology, severity, fibrosis

DOI: 10.3233/JND-221547

Journal: Journal of Neuromuscular Diseases, vol. 10, no. 1, pp. 155-158, 2023