Save the mouse! Non-lethal, repeated blood transcriptome profiling in murine disease models 3386

Abstract Description Murine disease models can reveal mechanisms and allow testing of drug/vaccine interventions. Current approaches often rely on evaluation after euthanasia, with large numbers of animals needed for time course and dose-response studies. Measuring blood transcriptome biomarkers in small volumes (serially) could provide useful insights and reduce the number of animals needed. We evaluated the utility of repeated (non-lethal) small-volume blood sampling for profiling RNA expression in the same mice at different stages of tuberculosis progression and treatment: 1) before infection (day 0), 2) at the peak of infection (d30 after infection), 3) after 10 weeks of isoniazid (INH) treatment (days 30-99 post-infection), and 4) after partial INH treatment (days 30-70 post-infection) to allow relapse (days 70 – 99 post-infection). We isolated RNA from 100 uL of whole blood for transcriptome profiling using the DriverMap™ assay for quantitation of ∼4700 key mouse genes using a targeted sequencing panel. Blood transcriptome profiling showed abundant up-regulation of immune and inflammatory genes at d30 after infection (e.g. 571DEGs). Additional changes were found after either complete or partial INH treatment (e.g. complete vs d30 after infection: 321DEGs). The data reveal heterogeneity in responses & allow comparisons using each mouse as its own control. Transcriptome profiling using non-terminal, serial blood samples can inform biomarker discovery/monitoring & reduce animal use & costs. Topic Categories Technological Innovations in Immunology (TECH)