Aims: Reduced sialic acid might have an impact on the ageing skeletal muscle in the heterozygous UDP-N-Acetylglucosamine2-Epimerase/N-Acetylmannosamine kinase GNE knock out mouse model (C57Bl/6 GNE±) compared to wildtype (C57Bl/6 GNE+/+), mimicking a carrier status of autosomal-recessive hereditary inclusion body myositis.
Methods: Mice were analysed after 24 weeks (n=9 C57Bl/6 GNE+/+, n=7 C57Bl/6 GNE±) and after 80 weeks (n=10 C57Bl/6 GNE+/+, n=12 C57Bl/6 GNE±) for clinical phenotype, creatine kinase (CK) levels, histopathological changes by light and electron microscopy, and membrane bound sialic acid concentration in skeletal muscle.
Results: C57Bl/6 GNE±had a 20% lower performance in the treadmill exercise than C57Bl/6 GNE±. There was no higher mortality rate between the groups until 80 weeks. Aged muscle showed mild myopathic changes at week 80 in both groups. There was no difference in the clinical appearance (e.g. muscle weight, CK levels) and the histopathological features. Electrone microscopy showed paranuclear vacuoles in both C57Bl/6 GNE+/+ and C57Bl/6 GNE+/+. Sialic acid was 33–53% lower at week 24 and 12–15% at week 80 in C57Bl/6 GNE±compared to C57Bl/6 GNE+/+ The membrane bound sialic acid concentration increased over time by 16–46% in C57Bl/6 GNE+/+, but by 87–207% in C57Bl/6 GNE±.
Conclusions: The C57Bl/6 GNE±did not develop any specific phenotype. The vacuoles in both heterozygous and wildtype mice rather reflect ageing processes in skeletal muscle. The functional importance of increased sialic acid concentration in ageing muscle is not clear.
