Genetic Background Effects on Disease Onset and Lifespan of the Mutant Dynactin p150Glued Mouse Model of Motor Neuron Disease.
PLoS One 2015 Mar 12; 10(3):e0117848
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily affecting motor neurons in the central nervous system. Although most cases of ALS are sporadic, about 5-10% of cases are familial (FALS) with approximately 20% of FALS caused by mutations in the Cu/Zn superoxide dismutase (SOD1) gene. We have reported that hSOD1-G93A transgenic mice modeling this disease show a more severe phenotype when the transgene is bred on a pure SJL background and a milder phenotype when bred on a pure B6 background and that these phenotype differences link to a region on mouse Chromosome 17.To examine whether other models of motor neuron degeneration are affected by genetic background, we bred the mutant human dynactin p150Glued (G59S-hDCTN1) transgene onto inbred SJL and B6 congenic lines. This model is based on an autosomal dominant lower motor neuron disease in humans linked to a mutation in the p150Glued subunit of the dynactin complex. As seen in hSOD1-G93A mice, we observed a more severe phenotype with earlier disease onset. PLoS One 2015 Mar 12; 10(3):e0117848
Heiman-Patterson, Terry D; Blankenhorn, Elizabeth P; Sher, Roger B; Jiang, Juliann; Welsh, Priscilla; Dixon, Meredith C; Jeffrey, Jeremy I; Wong, Philip; Cox, Gregory A.; and Alexander, Guillermo M, "Genetic Background Effects on Disease Onset and Lifespan of the Mutant Dynactin p150Glued Mouse Model of Motor Neuron Disease." (2015). Faculty Research 2015. 43.