Skeletal-Muscle Glutamate-Ammonia Ligase as Potential Biomarker of Preclinical Prion Diseases

We provide here a comprehensive transcriptional profiling of murine blood, spleen and skeletal muscle and brain on eight different time points after intracerebral prion inoculation. Our findings provide a detailed time course of extra-neural, transcriptional changes during prion disease which we presume to be of immediate relevance for biomarker development. Data analysis scripts can be found on https://github.com/marusakod/RML_extraneural_organs. Six-week-old (main and validaition cohort) C57BL/6 mice were inoculated in the right hemisphere . For prion inoculations, 30 μl of RML6 (passage 6 of Rocky Mountain Laboratory strain mouse-adapted scrapie prions) at a 10−2 dilution of a 10% homogenate, containing 9.02 log LD50 of infectious units per ml in 10% homogenate. Control inoculations were performed using 30 μl of non-infectious brain homogenate (NBH) from CD-1 mice at the same dilution. Each timepoint and treatment group (n = 44 different treatment groups) entails at least 3 and up to 6 animals, except for brains from NBH-inoculated animals at 20 weeks post inoculation (n = 2).