Unknown

Dataset Information

0

Overexpression of CCS in G93A-SOD1 mice leads to accelerated neurological deficits with severe mitochondrial pathology.


ABSTRACT: Cu, Zn superoxide dismutase (SOD1) has been detected within spinal cord mitochondria of mutant SOD1 transgenic mice, a model of familial ALS. The copper chaperone for SOD1 (CCS) provides SOD1 with copper, facilitates the conversion of immature apo-SOD1 to a mature holoform, and influences in yeast the cytosolic/mitochondrial partitioning of SOD1. To determine how CCS affects G93A-SOD1-induced disease, we generated transgenic mice overexpressing CCS and crossed them to G93A-SOD1 or wild-type SOD1 transgenic mice. Both CCS transgenic mice and CCS/wild-type-SOD1 dual transgenic mice are neurologically normal. In contrast, CCS/G93A-SOD1 dual transgenic mice develop accelerated neurological deficits, with a mean survival of 36 days, compared with 242 days for G93A-SOD1 mice. Immuno-EM and subcellular fractionation studies on the spinal cord show that G93A-SOD1 is enriched within mitochondria in the presence of CCS overexpression. Our results indicate that CCS overexpression in G93A-SOD1 mice produces severe mitochondrial pathology and accelerates disease course.

SUBMITTER: Son M 

PROVIDER: S-EPMC1851618 | BioStudies | 2007-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC2431012 | BioStudies
1000-01-01 | S-EPMC2900889 | BioStudies
2011-01-01 | S-EPMC3116235 | BioStudies
1000-01-01 | S-EPMC5264640 | BioStudies
2010-01-01 | S-EPMC3000256 | BioStudies
2011-01-01 | S-EPMC3024775 | BioStudies
2002-01-01 | S-EPMC107843 | BioStudies
2018-01-01 | S-EPMC6180298 | BioStudies
| S-SCDT-EMM-2018-08888 | BioStudies
1000-01-01 | S-EPMC5056396 | BioStudies