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Microglia-Specific Promoter Activities of HEXB Gene

Shah, Sahil
; 
Wong, Lilly M.
; 
Ellis, Kendra
; ; 
Saribas, Sami
; 
Ting, Julia
; 
Wei, Zhengyu
; 
Tang, Yuyang
; 
Wang, Xianwei
; ... show 5 more
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Genre
Journal article
Date
2022-03-10
Advisor
Committee member
Group
Center for Metabolic Disease Research (Temple University)
Department
Pathology and Laboratory Medicine
Cardiovascular Sciences
Subject
HexB
 CD68
 Microglia
 Astrocytes
 Gene therapy
 Gene editing
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http://hdl.handle.net/20.500.12613/9476
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ShahEtAl-JournalArticle-2022-03.pdf
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http://dx.doi.org/10.3389/fncel.2022.808598
Abstract
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 HEXB 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 Hexb gene. The native promoter region of mouse, human, and monkey HEXB 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 CD68 gene that was highly active in microglia but not in astrocytes. Considering that HEXB is specifically expressed in microglia, these data suggest that the newly characterized microglia-specific HEXB minimal/native promoter can be an ideal candidate for microglia-targeting AAV gene therapy in the CNS.
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Citation
Shah S, Wong LM, Ellis K, Bodnar B, Saribas S, Ting J, Wei Z, Tang Y, Wang X, Wang H, Ling B, Margolis DM, Garcia JV, Hu W and Jiang G (2022) Microglia-Specific Promoter Activities of HEXB Gene. Front. Cell. Neurosci. 16:808598. doi: 10.3389/fncel.2022.808598
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Frontiers Media
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Frontiers in Cellular Neuroscience, Vol. 16
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