use of temperature for standardizing the progression of francisella tularensis in mice使用温度标准化土拉杆菌内老鼠的进展.pdfVIP

Use of Temperature for Standardizing the Progression of Francisella tularensis in Mice 1 1 1 1 2 Claudia R. Molins *, Mark J. Delorey , John W. Young , Brook M. Yockey , John T. Belisle , Martin E. Schriefer1, Jeannine M. Petersen1 1 Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, United State of America, 2 Microbiology, Immunology, and Pathology Department, Colorado State University, Fort Collins, Colorado, United States of America Abstract The study of infectious agents, their pathogenesis, the host response and the evaluation of newly developed countermeasures often requires the use of a living system. Murine models are frequently used to undertake such investigations with the caveat that non-biased measurements to assess the progression of infection are underutilized. Instead, murine models predominantly rely on symptomology exhibited by the animal to evaluate the state of the animal’s health and to determine when euthanasia should be performed. In this study, we used subcutaneous temperature as a non- subjective measurement to follow and compare infection in mice inoculated with Francisella tularensis, a Gram-negative pathogen that produces an acute and fatal illness in mice. A reproducible temperature pattern defined by three temperature phases (normal, febrile and hypothermic) was identified in all mice infected with F. tularensis, regardless of the infecting strain. More importantly and for the first time a non-subjective, ethical, and easily determined surrogate endpoint for death based on a temperature, termed drop point, was identifi