AstroGreen transgenic mouse illuminates the trafficking of astrocyte-derived extracellular vesicles

Nieland, L.; Abou Haidar, E.; Rufino-Ramos, D.; Prabhakar, S.; Samaha, Y.; Breyne, K.; Fordjour, F.K.; Broekman, M.L.D.; Gould, S.; Breakefield, X.O.; Abels, E.R.

doi:doi:10.1016/j.mcn.2025.104051

Astrocytes interact with neighboring cells by releasing extracellular vesicles (EVs). Tools to study astrocyte EVmediated communication with other brain cells in vivo are essential. In this study, we crossed the Exomap1 transgenic mouse expressing Cre-activated human-specific CD81 (HsCD81) fused to the fluorescent protein mNeonGreen (HsCD81mNG), to a transgenic mouse expressing Cre under the astrocyte-expressing GFAP promoter resulting in Exomap1::Gfap-Cre mice, referred to here as AstroGreen. We characterized HsCD81mNG-expressing astrocytes and shedded EVs loaded with HsCD81mNG and Cre, both in vitro and in mouse brains. Using this model, we show that HsCD81mNG can be used to track EV content, production, and functional Cre transfer in vitro and in the brain, allowing evaluation of the interaction of astrocytes with neighboring cells mediated by EVs. We anticipate that this model will improve our understanding of astrocytes transferring EVs within their surroundings during normal...Show moreAstrocytes interact with neighboring cells by releasing extracellular vesicles (EVs). Tools to study astrocyte EVmediated communication with other brain cells in vivo are essential. In this study, we crossed the Exomap1 transgenic mouse expressing Cre-activated human-specific CD81 (HsCD81) fused to the fluorescent protein mNeonGreen (HsCD81mNG), to a transgenic mouse expressing Cre under the astrocyte-expressing GFAP promoter resulting in Exomap1::Gfap-Cre mice, referred to here as AstroGreen. We characterized HsCD81mNG-expressing astrocytes and shedded EVs loaded with HsCD81mNG and Cre, both in vitro and in mouse brains. Using this model, we show that HsCD81mNG can be used to track EV content, production, and functional Cre transfer in vitro and in the brain, allowing evaluation of the interaction of astrocytes with neighboring cells mediated by EVs. We anticipate that this model will improve our understanding of astrocytes transferring EVs within their surroundings during normal physiological processes and in the context of neuropathological conditions.Show less

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AstroGreen transgenic mouse illuminates the trafficking of astrocyte-derived extracellular vesicles