Aartsma-Rus Annemieke, van Putten Maaike, Mantuano Paola, De Luca Annamaria
Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Department of Pharmacy-Drug Sciences, Section of Pharmacology, University of Bari "Aldo Moro", Bari, Italy.
J Neuromuscul Dis. 2023;10(1):155-158. doi: 10.3233/JND-221547.
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.
几十年来，研究人员一直使用C57BL/10ScSn-Dmdmdx/J（mdx）小鼠模型来研究杜氏肌营养不良症的病理学并开发治疗方法。然而，与人类情况相比，该模型受到的影响相对较轻。最近，有人提出D2.B10-Dmdmdx/J（D2.mdx）小鼠模型受到的影响更严重，因此是更好的替代模型。虽然该模型的病理学在生命早期确实更为明显，但它不会进展，而且越来越多的证据表明，它实际上会随着年龄的增长而部分缓解。因此，在使用该模型时需要谨慎。然而，作为TREAT-NMD治疗咨询委员会（TACT）的临床前专家，我们经常遇到低估这一注意事项的研究设计。我们在此提供相关背景信息，说明在当前知识阶段如何最好地使用这两种模型进行临床前研究。
