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A new colony of mdx dystrophic mice with genetically identical littermate controls

S.L. Kueh, S.I. Head, J.W. Morley, Physiology, School of Medical Sciences, Sydney, NSW, Australia

The mdx mouse and boys with Duchenne Muscular Dystrophy (DMD) both lack a functional copy of the protein dystrophin and the absence of dystrophin is the primary cause of the pathophysiology seen in DMD. The dystrophinopathies arise as a result of a mutation of a single “dystrophin” gene on the X chromosome. The mdx mouse is the most commonly used animal model of DMD, in part because it is a convenient and economical model and also because the original mouse homozygous/hemizygous cross in this X-linked condition meant that all the off spring were homo- or hemi- zygous for the mdx mutation. The mdx mouse was identified as a spontaneous mutation in 1984.   Since then all studies involving mdx mice have used mice from a separate wild type colony as controls ( C57B1/10 ScSn or similar). This leaves studies on the mdx mouse open to the criticism that after 20 years of separate breeding that the controls and mdx mice may have a different genetic background and that any reported difference could be the result of a genetic mutation other than the one on the dystrophin gene.  As a result of this criticism of the controls used in mdx work at least one major journal will not accept mdx studies unless littermate controls are used. In order to solve this problem we have generated a new line of mdx mice (N1F1 mdx mice). Male C57BL/10ScSn-Dmd (mdx) were bred with female C57BL/10ScSn mice, the offspring produced were mated together to produce the following offspring: 50% females homozygous (mdx/mdx); 50% females heterozygous (mdx/+); 50% males hemizygous (mdx/Y) and  50% males wild type (+/Y).  In this study we show that the litter mates can be conveniently phenotyped by one or more of the following methods, serum creatine kinase measurements, skeletal muscle histology and/or western blots for dystrophin using a polyclonal dystrophin antibody.  All animals were killed with Halothane prior to removing tissue. N1F1 mice are a cheap and convenient method of generating male mdx mice with male litter mate controls on a genetically identical background.