These Cmah-mdx mutant mice harbor two mutations; the Cmah knockout allele (Cmah^tm1Avrk) and the spontaneous X-linked muscular dystrophy mutation (Dmd^mdx). The Cmah knockout allele abolishes Cmah expression; eliminating biosynthesis of N-glycolylneuraminic acid (Neu5Gc) from all cells and mimicking the normal human lack of functional CMAH.
The Dmd^mdx mutation abolishes dystrophin expression and models Duchenne muscular dystrophy (DMD) with less severe myopathology.

Compared to homozygous mdx mice (Dmd^mdx/mdx females / Dmd^mdx/Y males), Cmah-deficiency in homozygous Cmah-mdx mice (Cmah^-/-;Dmd^mdx/mdx females / Cmah^-/-;Dmd^mdx/Y males) results in accelerated age of onset, rate of progression, and severity of the major DMD phenotypes contributing to morbidity and mortality. This is especially true for loss of ambulation, cardiac and respiratory muscle weakness, and loss of lifespan. Homozygous Cmah-mdx mice also exhibit diminished expression/function of the dystrophin-associated glycoprotein (DAG) complex and increased activation of complement. Specifically, homozygous Cmah-mdx mice have Neu5Gc accumulation into small regenerating muscles in dystrophic regions. Some homozygous Cmah-mdx mice exhibit serum antibodies to Neu5Gc and increased classical complement Neu5Gc-dependent killing of muscle cells. The donating investigator reports one can successfully breed Cmah^-/-;Dmd^mdx/mdx females with Cmah^-/-;Dmd^mdx/Y males if the mice are young (starting at 6-8 weeks old).

Heterozygous Cmah-mdx mice (Cmah^+/-;Dmd^mdx/mdx females / Cmah^+/-;Dmd^mdx/Y males) are viable and fertile. The donating investigator reports heterozygous Cmah-mdx mice exhibit the same phenotypic traits as homozygous mdx mice (Dmd^mdx/mdx females / Dmd^mdx/Y males).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for these mice. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available. To view the phenotype describing the Cmah knockout mice a C57BL/6 genetic background, please see Stock No. 017588. To view the phenotype describing the mdx mutant mice on a C57BL/10ScSn genetic background, please see Stock No. 001801.