Production of a canine model of Parkinson’s disease using somatic cell nuclear transfer

Dogs have been considered a suitable model to study human neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease (PD), and brain aging, because of their long lifespan and the similarities of disease presentation and clinical response in humans and dogs. Further, it is possible to evaluate the visible cognition/motion ability of patients with brain dysfunction. In the present study, we aimed to generate a canine model of PD that overexpresses the human DJ-1 (hDJ-1) gene using the somatic cell nuclear transfer (SCNT) technique. The hDJ-1 gene was transfected into canine fetal fibroblasts, which were used to produce cloned embryos. Reconstructed embryos were transferred into the oviduct of surrogate mothers, one of which gave birth to one dog. The cloned dog was depressed, and his movements were slow and fewer, resulting in an abnormal phenotype, as observed via imaging analyses, such as positron emission tomography (PET) and magnetic resonance imaging (MRI) analyses; these findings were similar to the symptoms of PD in humans. In addition, exogenous hDJ-1 was successfully transmitted to the next generation without silencing. We confirmed that the puppies exhibited the same behavior and imaging analysis as the hDJ-1 transgenic (TG) dog. Using SCNT, we generated TG dogs with PD that overexpressed the hDJ-1 gene. Human PD-like phenotypes have been confirmed in the TG dogs. To the best of our knowledge, this is the first report that describes the establishment of a canine model of PD. Furthermore, TG dogs could be used in preclinical trials of drugs for the treatment of PD.