Stable, neuron-specific gene expression in the mouse brain

Osama Ahmed; Kingsley M Ekumi; Francesco V Nardi; Gulimiheranmu Maisumu; Khaled Moussawi; Eric D Lazartigues; Bo Liang; Abraam M Yakoub

doi:10.1186/s13036-023-00400-5

Stable, neuron-specific gene expression in the mouse brain

J Biol Eng. 2024 Jan 16;18(1):8. doi: 10.1186/s13036-023-00400-5.

Authors

Osama Ahmed^{1

2}, Kingsley M Ekumi², Francesco V Nardi^{1

2}, Gulimiheranmu Maisumu^{1

2}, Khaled Moussawi³, Eric D Lazartigues^{4

5}, Bo Liang², Abraam M Yakoub⁶

Affiliations

¹ Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, USA.
² Biomedical Engineering Program, University of North Dakota, Grand Forks, ND, USA.
³ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
⁵ Southeast Louisiana Veterans Healthcare System, New Orleans, LA, USA.
⁶ Department of Medicine, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, USA. ayakoub@bwh.harvard.edu.

Abstract

Gene delivery to, and expression in, the mouse brain is important for understanding gene functions in brain development and disease, or testing gene therapies. Here, we describe an approach to express a transgene in the mouse brain in a cell-type-specific manner. We use stereotaxic injection of a transgene-expressing adeno-associated virus into the mouse brain via the intracerebroventricular route. We demonstrate stable and sustained expression of the transgene in neurons of adult mouse brain, using a reporter gene driven by a neuron-specific promoter. This approach represents a rapid, simple, and cost-effective method for global gene expression in the mouse brain, in a cell-type-specific manner, without major surgical interventions. The described method represents a helpful resource for genetically engineering mice to express a therapeutic gene, for gene therapy studies, or to deliver genetic material for genome editing and developing knockout animal models.

Keywords: Brain; Brain disease; Gene delivery; Gene expression; Gene therapy; Genetic engineering.