Research Article
A Mathematical Model of Skeletal Muscle Disease and Immune
Response in the mdx Mouse
Abdul Salam Jarrah,
1
Filippo Castiglione,
2
Nicholas P. Evans,
3
Robert W. Grange,
4
and Reinhard Laubenbacher
5,6
1
Department of Mathematics and Statistics, American University of Sharjah, Sharjah 26666, UAE
2
Institute for Applied Mathematics, National Research Council of Italy, 00185 Rome, Italy
3
Department of Population Health Sciences, Virginia Tech, Blacksburg, VA 24060, USA
4
Department of Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg, VA 24060, USA
5
Center of Quantitative Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
6
Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA
Correspondence should be addressed to Abdul Salam Jarrah; ajarrah@aus.edu
Received 30 March 2014; Accepted 19 May 2014; Published 11 June 2014
Academic Editor: Francesco Pappalardo
Copyright © 2014 Abdul Salam Jarrah et al. his is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Duchenne muscular dystrophy (DMD) is a genetic disease that results in the death of afected boys by early adulthood. he genetic
defect responsible for DMD has been known for over 25 years, yet at present there is neither cure nor efective treatment for
DMD. During early disease onset, the mdx mouse has been validated as an animal model for DMD and use of this model has
led to valuable but incomplete insights into the disease process. For example, immune cells are thought to be responsible for a
signiicant portion of muscle cell death in the mdx mouse; however, the role and time course of the immune response in the
dystrophic process have not been well described. In this paper we constructed a simple mathematical model to investigate the role
of the immune response in muscle degeneration and subsequent regeneration in the mdx mouse model of Duchenne muscular
dystrophy. Our model suggests that the immune response contributes substantially to the muscle degeneration and regeneration
processes. Furthermore, the analysis of the model predicts that the immune system response oscillates throughout the life of the
mice, and the damaged ibers are never completely cleared.
1. Background
Duchenne muscular dystrophy (DMD) is a lethal, X-
chromosome muscle wasting disease afecting approximately
one in 3,500 boys [1, 2]. Patients appear clinically normal at
birth with the exception of elevated serum creatine kinase
levels. he onset of DMD begins in early childhood with the
irst observed symptoms between two and ive years of age.
Typically by the age of 12, DMD patients require the use of
a wheelchair due to the loss of lower limb muscle strength.
Progressive weakness of the arms and legs, along with
kyphoscoliosis, continues through late disease progression.
Many patients die in their late teens or early twenties due to
respiratory or cardiac complications [1, 3]. Currently, there
are no efective means of therapy or treatment for DMD.
In 1984, Bulield et al. identiied a spontaneous mutation
in C57BL/10ScSn inbred mice that exhibited a disease state
similar to human DMD [4]. he X chromosome-linked
mutation resulted in mice (mdx mice) with high serum levels
of muscle enzymes and with histological lesions comparable
to those seen in human muscular dystrophy. his mutation in
the murine dystrophin gene caused an absence of dystrophin
in skeletal muscle and this key defect validated the mdx
mouse as a suitable model of the early onset of DMD human
disease [5, 6].
he histology and time course of the disease in mdx
mouse model are very diferent from those in DMD patients:
relatively normal life span and overall itness compared to
progressive physical impairment leading to death in DMD
patients [7]. Nonetheless, the mdx mouse model is regarded
Hindawi Publishing Corporation
BioMed Research International
Volume 2014, Article ID 871810, 11 pages
http://dx.doi.org/10.1155/2014/871810