Article originally posted at Alzheimer Research Forum.
14 September 2012. A nagging problem with many Parkinson’s mouse models is their failure to capture neuron loss, a critical feature of this disease. Case in point: People with loss-of-function mutations in the DJ-1 gene (aka PARK7) develop a rare, recessive form of parkinsonism with profound dopaminergic neurodegeneration (Bonifati et al., 2003; Hague et al., 2003), yet DJ-1 knockout mice on various backgrounds have no appreciable cell loss. Curiously, a subset of DJ-1-null mice has now emerged with the desired phenotype—age-dependent, unilateral loss of dopaminergic neurons in PD-affected brain areas, followed by mild motor symptoms. The serendipitous discovery, reported online September 10 in the Proceedings of the National Academy of Sciences USA, came as David Park, University of Ottawa, Canada, and colleagues were backcrossing DJ-1 knockouts onto a C57 wild-type background.
While these mice do model key events in the human disease, they lack α-synuclein pathology—a hallmark of the sporadic form of Parkinson’s that accounts for more than 90 percent of cases. The genetic basis for the new model remains unclear, but further studies with these animals could identify potential modifier genes for the DJ-1-related degenerative phenotype.