Title
Genetic Background Effects on Disease Onset and Lifespan of the Mutant Dynactin p150Glued Mouse Model of Motor Neuron Disease.
Document Type
Article
Publication Date
3-12-2015
JAX Source
PLoS One 2015 Mar 12; 10(3):e0117848
Volume
10
Issue
3
First Page
0117848
Last Page
0117848
ISSN
1932-6203
PMID
25763819
Abstract
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
Recommended Citation
Heiman-Patterson T,
Blankenhorn E,
Sher R,
Jiang J,
Welsh P,
Dixon M,
Jeffrey J,
Wong P,
Cox GA,
Alexander G.
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