Species-dependent neuropathology in transgenic SOD1 pigs

Huaqiang Yang, Guohao Wang, Haitao Sun, Runzhe Shu, Tao Liu, Chuan-En Wang, Zhaoming Liu, Yu Zhao, Bentian Zhao, Zhen Ouyang, Dongshan Yang, Jiao Huang, Yueling Zhou, Shinhua Li, Xiaodan Jiang, Zhi-Cheng Xiao, Xiao-Jiang Li, Liangxue Lai

Research output: Contribution to journalArticleResearchpeer-review

44 Citations (Scopus)


Mutations in the human copper/zinc superoxide dismutase 1 (hSOD1) gene cause familial amyotrophic lateral sclerosis (ALS). It remains unknown whether large animal models of ALS mimic more pathological events seen in ALS patients via novel mechanisms. Here, we report the generation of transgenic pigs expressing mutant G93A hSOD1 and showing hind limb motor defects, which are germline transmissible, and motor neuron degeneration in dose- and age-dependent manners. Importantly, in the early disease stage, mutant hSOD1 did not form cytoplasmic inclusions, but showed nuclear accumulation and ubiquitinated nuclear aggregates, as seen in some ALS patient brains, but not in transgenic ALS mouse models. Our findings revealed that SOD1 binds PCBP1, a nuclear poly(rC) binding protein, in pig brain, but not in mouse brain, suggesting that the SOD1-PCBP1 interaction accounts for nuclear SOD1 accumulation and that species-specific targets are key to ALS pathology in large mammals and in humans.
Original languageEnglish
Pages (from-to)464 - 481
Number of pages18
JournalCell Research
Issue number4
Publication statusPublished - 2014

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