Functional analysis of Gpnmb gene in Alzheimer's disease model mice
Proceedings for Annual Meeting of The Japanese Pharmacological Society(2020)
摘要
The onset and progression of Alzheimer's disease (AD) correlate with neuroinflammatory processes, and inflammatory microglia (MG) are associated with AD-like pathology in a transgenic mouse model. We recently developed a novel monoclonal antibody, 9F5, against one subtype (type 1) of rat primary MG, and identified the antigen molecule for 9F5: truncated form of rat GPNMB/osteoactivin (Kawahara et al., GLIA, 2016). However, the distribution and function of GPNMB+ type 1 MG in AD brain are largely unknown. In the present study, we observed GPNMB+Iba1+ MG surrounding Aβ plaque in neocortex of amyloid precursor protein (APP23) transgenic mice. In addition, GPNMB+Iba1+ MG were observed in non-plaque areas of hippocampus of APP23 mice. We generated Gpnmb knockout mice to investigate the functional relevance of GPNMB for microglia in vivo. Homozygous Gpnmb-KO mice did not show any growth retardation including body weight loss, and the fertility was normal. We observed that AD-related brain dysfunction in APP23 and 5xFAD mice were regulated by Gpnmb gene dosage. These finding suggest that GPNMB-positive type 1 MG may play a role in regulation of neuropathological process of AD.
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