Rederivation of transgenic rodent models expressing disease modified tau protein - a report

摘要

Transgenic animals are used extensively as in vivo experimental systems for modelling human diseases. A prerequisite for obtaining reliable experimental results is that the animal models used are free of defined infectious agents, including those that rarely produce disease, but still can modulate immune responses and alter the phenotype of affected animals. We have recently rederived transgenic rodent models of tauopathy to meet specific-pathogen free health standards for breeding in barrier areas. The surgical implantation of 2- cell embryos in three transgenic rat lines SHR24, SHR72 and W72 resulted in a total of 86 pups, out of which 36 were positive for transgene (42% efficiency). An overall 48 % transgenic efficiency was achieved in two transgenic mice lines R3m/4 and R3m/7 following non-surgical transfer of embryos. Microbiological evaluation, based on sentinel screening and serological examinations, confirmed the SPF status of all rederived strains. Most importantly, all rederived transgenic rodents developed AT8 positive neurofibrillary structures demonstrating high reproducibility of the phenotype. To the best of our knowledge, this report is the first on rederivation of transgenic models of human tauopathy.