The hGFAP-driven conditional TSPO knockout is protective in a mouse model of multiple sclerosis
Open accessAbstract
The mitochondrial translocator protein (TSPO) has been implicated in CNS diseases. Here, we sought to determine the specific role of TSPO in experimental autoimmune encephalomyelitis (EAE), the most studied animal model of multiple sclerosis (MS). To fundamentally elucidate the functions of TSPO, we first developed a viable TSPO knockout mouse. A conditional TSPO knockout mouse was generated by utilizing the Cre-Lox system. We generated a TSPO floxed mouse and then crossed this mouse with a Cre recombinase expressing mouse driven by the human glial fibrillary acidic protein (hGFAP) promoter. The resultant mouse was a neural linage line specific TSPO knockout. The loss of TSPO in the CNS did not result in overt developmental defects or phenotypes. The TSPO−/− mouse showed a decrease in GFAP expression, correlating with a decrease in astrogliosis in response to neural injury during EAE. This decrease in astrogliosis was also witnessed in the lessening of severity of EAE clinical scoring, indicating an in vivo functional role for TSPO in suppressing EAE. The TSPO−/− mouse could be a useful tool in better understanding the role of TSPO in CNS disease and our results implicate TSPO as a potential therapeutic target in MS.
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The human GFAP-driven conditional knockout of TSPO in mice resulted in significantly reduced severity of experimental autoimmune encephalomyelitis.
“The human GFAP-driven conditional knockout of TSPO in mice resulted in significantly reduced severity of experimental autoimmune encephalomyelitis (Daugherty et al., 2016).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Daugherty et al., 2016
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- Authors
- Daugherty, D. J., Chechneva, O., Mayrhofer, F., & Deng, W.
- Affiliations
- University of California, Davis (US)
- Shriners Hospitals for Children - Northern California (US)
- Corresponding author
- Deng, Wenbin
- Venue
- Scientific Reports
- Published
- 2016-03-01
- Volume
- 6
- Issue
- 1
- Pages
- 22556-22556
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4772008
- OpenAlex
- W2306146832
- Cited by
- 36
- References
- 21
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 4
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Shriners Hospitals for Children
- Multiple Sclerosis Society
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS059043)
- National Institute of Environmental Health Sciences (R01ES015988)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- translocator protein (TSPO), multiple sclerosis, experimental autoimmune encephalomyelitis, conditional knockout mice, astrocytes, astrocyte activation, GFAP expression, neuroprotection, therapeutic target, mitochondrial proteins
- MeSH terms
- Animals, Central Nervous System, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Female, Glial Fibrillary Acidic Protein, Inflammation, Mice, Inbred C57BL, Multiple Sclerosis, Promoter Regions, Genetic, RNA, Messenger, Tumor Necrosis Factor-alpha, Receptors, GABA, Mice, Knockout, Mice, Chemokine CXCL10
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