Genetic background effects on disease onset and lifespan of the mutant dynactin p150Glued mouse model of motor neuron disease

PloS One
Terry D Heiman-PattersonGuillermo M Alexander

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 (p<0.001) and decreased survival (p<0.00001) when the G59S-hDCTN1 transgene was bred onto the SJL background and delayed onset (p<0.0001) with increased survival (p<0.00001) when bred onto the B6 backg...Continue Reading

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Citations

Jul 3, 2016·Brain : a Journal of Neurology·Gen ShiihashiNorihiro Suzuki
Dec 7, 2018·Human Molecular Genetics·Liang QiangPeter W Baas
Oct 6, 2017·Nature Reviews. Disease Primers·Orla HardimanLeonard H van den Berg
Feb 14, 2021·Cells·Sara Marmolejo-Martínez-ArteseroDavid Romeo-Guitart

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Methods Mentioned

BETA
transgenic
PCR

Software Mentioned

SYSTAT

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