A major QTL on mouse chromosome 17 resulting in lifespan variability in SOD1-G93A transgenic mouse models of amyotrophic lateral sclerosis

• DOI: 10.3109/21678421.2014.932381
• Publication Date: 2014-07-10T10:19:33Z
• Authors: Roger B. Sher; Terry D. Heiman-P...; Elizabeth A. Blan...; Juliann Jiang; Guillermo Alexander; Jeffrey S. Deitch; Gregory A. Cox
• Keywords: Genetic architecture; C9ORF72; Chromosome 4

AbstractAmyotrophic lateral sclerosis is a late-onset degenerative disease affecting motor neurons in the spinal cord, brainstem, and cortex. There great variation expression of ALS symptoms even between siblings who both carry same Cu/Zn superoxide dismutase (SOD1) mutations. One important use transgenic mouse models SOD1-ALS study genetic influences on severity. We utilized multiple inbred strains containing SOD1-G93A transgene to demonstrate major quantitative trait locus (QTL) chromosome 17 resulting significant shift lifespan. Reciprocal crosses long- short-lived identified critical regions, we have narrowed area for potential modifier(s) < 2Mb genome. Results showed that resequencing this region resulted 28 candidate genes with potentially functional differences strains. In conclusion, these studies provide first modifier lifespan model FALS and, once identified, may insight into modifiers human most importantly, define new targets development therapies.Key words:: Amyotrophic sclerosisquantitative locilifespan Declaration interest: The authors report no conflicts interest. alone are responsible content writing paper.This work was supported by Hope Foundation (THP); DUCOM Cure Grant (THP, EPB, GAC, RS); Muscular Dystrophy Association (GAC).Notice correctionInformation regarding article were updated after published online.