Additional polgD257A mutation (mutator) does not influence dopaminergic neurodegeneration in aged parkin-deficient mice

Background: Parkinson’s disease is a neurodegenerative caused by the loss of dopaminergic neurons in substantia nigra pars compacta. Among first identified causes autosomal recessive were mutations parkin gene. Independently, we and other groups have developed various knockout mice, none displayed degeneration nigra. Interestingly, has been reported line (exon 3 deletion) carrying an additional mutation (D257A) mitochondrial DNA polymerase (polg) gene (mutator). The mutator mice show accelerated rates resulting premature-aging phenotype. Methods: To verify this finding, crossed our parkin-deficient with characterized phenotypic changes parkin/mutator double mutant up to one year age. We examined their locomotion motor coordination behaviors using open field, rotarod, pole test, subsequently investigating nigrostriatal axis counting TH-positive cells every tenth section throughout entire pas compacta termini striatum. Results: mutants did not display deficiencies behavior tests. could also detect neurodegeneration aged measured levels tyrosine hydroxylase positive as well striatal terminals. Conclusion: Our results do support hypothesis that polgD257A contributes age-related vulnerability mice. Keywords: Parkin, neurodegeneration, polgD257A, mutator,