#apaperaday: Cardiac and Skeletal Muscle Pathology in the D2/mdx Mouse Model and Caveats Associated with the Quantification of Utrophin.

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled:  Cardiac and Skeletal Muscle Pathology in the D2/mdx Mouse Model and Caveats Associated with the Quantification of Utrophin.

This pick is by Kennedy and Dugdale and it is selected for the considerations provided by the authors rather than the protocol itself on using d2/mdx mice. Doi: 10.1007/978-1-0716-2772-3_4

The mdx mouse in the black 10 background (mdx) has been around for decades. The mdx mouse in the diluted black agouti background (d2/mdx) is a new addition. It regenerates less well than mdx and is atrophic rather than hypertrophic. D2/mdx have an earlier onset of heart pathology than mdx, with ejection fraction reduction detectable by MRI and echo at 7 months. However in older wild type diluted black agouti mice there are heart problems as well.

When comparing d2/mdx with wild types the d2/mdx seems to get better heart function, but this may also be an artefact as wild type is getting worse so the difference decreases.

Authors outline that knowing this, one can still use the d2/mdx model but one has to be aware of the caveats. Agree with this and it is a similar message we had from the TREAT-NMD advisory committee for therapeutics.

Authors explain utrophin is expressed in the neuromuscular junction but also in muscle during development. When muscle is regenerating, utrophin will thus be upregulated. As mdx is regenerating constantly it is difficult to assess increases in utrophin (as a therapeutic approach).

Authors state d2/mdx is a better model for utrophin upregulation; it has less regeneration. Agree and had not considered this. The paper also contains protocols for staining for fibrosis and calcification if you are interested in those. I would like to thank the authors for their clearly outlined considerations on using d2/mdx or regular mdx.