BioProject

A deletion in the CMAH gene in humans occurred approximately 3.5 million years ago. More...

A deletion in the CMAH gene in humans occurred approximately 3.5 million years ago. This resulted in the inactivation of the CMP-Neu5Ac hydroxylase enzyme, and hence, in the specific deficiency in N-glycolylneuraminic acid (Neu5Gc), a form of sialic acid, in all modern humans. Although there is evidence that this molecular milestone in the origin of humans may have led to the evolution of human-specific pathogens, how deficiency in Neu5Gc might alter progression of non-infectious human diseases remains unanswered. Here, we have investigated cardiac and skeletal muscle gene expression changes in mdx mice, a model of Duchenne muscular dystrophy (DMD), that do or do not carry the human-like inactivating mutation in the mouse Cmah gene. We have evidence that Neu5Gc-deficiency in humans might explain some of the discrepancies in the disease phenotype between mdx mice and DMD patients. Overall design: The study had four groups of mice: 1) Wild type, 2) Cmah KO (mice carrying a human-like mutation in the Cmah gene and hence have human-like deficiency in Neu5Gc sialic acid), 3) mdx (mouse model for Duchenne Muscular Dystrophy), and 4) mdx mice deficient in Cmah. Gene expression was studied in heart and gastrocnemius muscle samples. Three replicates per group/tissue. Less...