Functional testing in mdx mice

Maurice Overzier, Netherlands

Research Technician

University of Bari “Aldo Moro”
Department of Pharmacy – Drug sciences

Maurice Overzier, research technician at the LUMC in Leiden, the Netherlands

From January 24th until January 30th I have visited the Section of Pharmacology in the University of Bari, where I was hosted by professor Annamaria De Luca to work with Dr. Anna Cozzoli.

The project I am currently working on focuses on developing antisense-mediated exon skipping using antisense oligonucleotides (AONs) as a potential therapy for Duchenne muscular dystrophy (DMD). Over the years, a wide variety of muscular dystrophy mouse models is being used to facilitate developing possible therapies and assessing typical phenotypes. One of these mouse models most commonly used is the mdx mouse. In order to aggravate the mild murine phenotype to better recapitulate the pathology observed in patients one can use forced exercise. This will allow more optimal pre-clinical evaluation of potential therapies. This forced treadmill exercise has been optimised and used for many years in the laboratory of prof. De Luca. In this protocol the mouse runs on a horizontal treadmill (Columbus Instruments, USA) for 30 minutes (twice a week) at a constant speed (12 meter/minute) (TREAT-NMD SOP: During my visit I witnessed exercise sessions. Functional tests, i.e. grip strength, the Rotarod and hanging tests, are additional in vivo tests used to assess the progression of the disease non-invasively. During my 5-day stay in Bari I have seen several in vivo functional tests, which are also used at the LUMC. One of these tests is the grip strength test (Columbus Instruments, USA) with which a mouse’s forelimb strength is measured quantitatively.

Looking at these assays being performed I have noticed several similarities compared to the setup in the LUMC. Small differences in the experiment (when comparing to the setup at the LUMC) were discussed. For example letting the mice get used to the treadmill by gradually increasing the speed (as a warm-up) and waiting a specific amount of time between grip strength measurements (with at least 1 min elapsing between each of the five determinations per animal).

After this STSM I can safely say that these experiments are performed in a more or less similar standard operating procedure, both in Bari and Leiden. Useful tips regarding these experiments were given and could be implemented in our current experimental setup. I am thankful for the opportunity to visit the lab in Bari and I have enjoyed their hospitality very much.

January 2015