Characterization of Muscle Histopathology in Aged Bmx Mice


Pre-Clinical Research

Poster Number: 225


Lilly Patneaude, University of Maryland, Nikki McCormack, PhD, Children's National Research Institute, Alyson Fiorillo, PhD, Children's National Medical Center (Washington, DC), Chris Heier, PhD, Children's National Medical Center

Title: `Characterization of Muscle Histopathology in Aged Bmx Mice
Author List: Lilly J. Patneaude1, Nikki M. McCormack1, Christopher R. Heier1,2, Alyson A. Fiorillo1,2

1Center for Genetic Medicine Research, Children’s National Medical Center, Washington, DC, USA

2Department of Genomics and Precision Medicine, The George Washington University, Washington, DC, USA

Becker muscular dystrophy (BMD) is an X-linked genetic disease caused by in-frame, partial loss-of-function mutations in the dystrophin (Dmd) gene. BMD is less severe than Duchenne muscular dystrophy (DMD), which is caused by a complete loss of the dystrophin protein. While significant progress has been made in DMD therapeutics, BMD continues to be understudied, with no current treatments. Recently, our lab generated the bmx (BMD X-linked) mouse model of BMD via CRISPR-induced deletion of dystrophin exons 45-47. We showed that bmx mice have impaired motor function, reduced dystrophin, increased myofiber size variability, and increased inflammation and fibrosis at 5 months of age. Here, we examined muscle histopathology in 2 year old wild-type, bmx, and mdx52 mice using hematoxylin and eosin (H&E) staining (necrosis and inflammation), sirius red fast green staining (fibrosis), and laminin staining (myofiber size). We found no increase in the area of inflammation and necrosis but observed an increase in fibrotic area in aged bmx muscle. Characterization of muscle histopathology in aged bmx mice will provide us with insights how to best approach new therapeutics.