Genetic ablation of Gpnmb does not alter synuclein-related pathology

NEUROBIOLOGY OF DISEASE

卷:159

Article

Brendza, Robert^1,5  Lin, Han¹  Stark, Kimberly¹  Foreman, Oded²  Tao, Janet²  Pierce, Andrew^2,6  Ngu, Hai²  Shen, Kimberle^1,7  Easton, Amy E.¹  Bhangale, Tushar³  Chang, Diana³  Bingol, Baris¹  Friedman, Brad A.⁴ 

[1] Genentech Inc, Dept Neurosci, San Francisco, CA USA

[2] Genentech Inc, Dept Pathol, San Francisco, CA USA

[3] Genentech Inc, Dept Human Genet, San Francisco, CA USA

[4] Genentech Inc, Dept OMNI Bioinformat, San Francisco, CA USA

[5] Nitrome Biosci, Belmont, CA USA

[6] 89Bio, San Francisco, CA USA

[7] Inst Mol & Cell Biol, Singapore, Singapore

关键词: Parkinson's disease;    Genetics;    GPNMB;    eQTL;    Phagocytosis;    Alpha synuclein;   

DOI  :  10.1016/j.nbd.2021.105494

来源: Elsevier

【 摘 要 】

The gene GPNMB is known to play roles in phagocytosis and tissue repair, and is upregulated in microglia in many mouse models of neurodegenerative disease as well as in human patients. Nearby genomic variants are associated with both elevated Parkinson's disease (PD) risk and higher expression of this gene, suggesting that inhibiting GPNMB activity might be protective in Parkinson's disease. We tested this hypothesis in three different mouse models of neurological diseases: a remyelination model and two models of alpha-synuclein pathology. We found that Gpnmb deletion had no effect on histological, cellular, behavioral, neurochemical or gene expression phenotypes in any of these models. These data suggest that Gpnmb does not play a major role in the development of pathology or functional defects in these models and that further work is necessary to study its role in the development or progression of Parkinson's disease.