Microglia-Specific Promoter Activities of HEXB Gene
Adeno-associated virus (AAV)-mediated genetic targeting of microglia remains a challenge. Overcoming this hurdle is essential for gene editing in the central nervous system (CNS). Here, we characterized the minimal/native promoter of the gene, which is known to be specifically and stably expressed i...
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Veröffentlicht in: | Frontiers in cellular neuroscience 2022-03, Vol.16, p.808598-808598 |
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Sprache: | eng |
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Zusammenfassung: | Adeno-associated virus (AAV)-mediated genetic targeting of microglia remains a challenge. Overcoming this hurdle is essential for gene editing in the central nervous system (CNS). Here, we characterized the minimal/native promoter of the
gene, which is known to be specifically and stably expressed in the microglia during homeostatic and pathological conditions. Dual reporter and serial deletion assays identified the critical role of the natural 5' untranslated region (-97 bp related to the first ATG) in driving transcriptional activity of the mouse
gene. The native promoter region of mouse, human, and monkey
are located at -135, -134, and -170 bp to the first ATG, respectively. These promoters were highly active and specific in microglia with strong cross-species transcriptional activities, but did not exhibit activity in primary astrocytes. In addition, we identified a 135 bp promoter of
gene that was highly active in microglia but not in astrocytes. Considering that
is specifically expressed in microglia, these data suggest that the newly characterized microglia-specific
minimal/native promoter can be an ideal candidate for microglia-targeting AAV gene therapy in the CNS. |
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ISSN: | 1662-5102 1662-5102 |
DOI: | 10.3389/fncel.2022.808598 |