Genetic ablation of Gpnmb does not alter synuclein-related pathology

Robert Brendza; Han Lin; Kimberly Stark; Oded Foreman; Janet Tao; Andrew Pierce; Hai Ngu; Kimberle Shen; Amy E. Easton; Tushar Bhangale; Diana Chang; Baris Bingol; Brad A. Friedman

Neurobiology of Disease (Nov 2021)

Genetic ablation of Gpnmb does not alter synuclein-related pathology

Robert Brendza,
Han Lin,
Kimberly Stark,
Oded Foreman,
Janet Tao,
Andrew Pierce,
Hai Ngu,
Kimberle Shen,
Amy E. Easton,
Tushar Bhangale,
Diana Chang,
Baris Bingol,
Brad A. Friedman

Affiliations

Robert Brendza: Department of Neuroscience, Genentech, Inc., South San Francisco, CA, USA
Han Lin: Department of Neuroscience, Genentech, Inc., South San Francisco, CA, USA
Kimberly Stark: Department of Neuroscience, Genentech, Inc., South San Francisco, CA, USA
Oded Foreman: Department of Pathology, Genentech, Inc., South San Francisco, CA, USA
Janet Tao: Department of Pathology, Genentech, Inc., South San Francisco, CA, USA
Andrew Pierce: Department of Pathology, Genentech, Inc., South San Francisco, CA, USA
Hai Ngu: Department of Pathology, Genentech, Inc., South San Francisco, CA, USA
Kimberle Shen: Department of Neuroscience, Genentech, Inc., South San Francisco, CA, USA
Amy E. Easton: Department of Neuroscience, Genentech, Inc., South San Francisco, CA, USA
Tushar Bhangale: Department of Human Genetics, Genentech, Inc., South San Francisco, CA, USA
Diana Chang: Department of Human Genetics, Genentech, Inc., South San Francisco, CA, USA
Baris Bingol: Department of Neuroscience, Genentech, Inc., South San Francisco, CA, USA; Corresponding authors at: Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
Brad A. Friedman: Department of OMNI Bioinformatics, Genentech, Inc., South San Francisco, CA, USA; Corresponding authors at: Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.

Journal volume & issue: Vol. 159
p. 105494

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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