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The Chx10-Traf3 Knockout Mouse as a Viable Model to Study Neuronal Immune Regulation
Journal article   Open access   Peer reviewed

The Chx10-Traf3 Knockout Mouse as a Viable Model to Study Neuronal Immune Regulation

Jami M. Gurley, Grzegorz B. Gmyrek, Elizabeth A. Hargis, Gail A. Bishop, Daniel J. J. Carr and Michael H. Elliott
Cells (Basel, Switzerland), Vol.10(8), p.2068
08/01/2021
DOI: 10.3390/cells10082068
PMCID: PMC8391412
PMID: 34440839
url
https://doi.org/10.3390/cells10082068View
Published (Version of record) Open Access

Abstract

Uncontrolled inflammation is associated with neurodegenerative conditions in central nervous system tissues, including the retina and brain. We previously found that the neural retina (NR) plays an important role in retinal immunity. Tumor necrosis factor Receptor-Associated Factor 3 (TRAF3) is a known immune regulator expressed in the retina; however, whether TRAF3 regulates retinal immunity is unknown. We have generated the first conditional NR-Traf3 knockout mouse model (Chx10-Cre/Traf3(f/f)) to enable studies of neuronal TRAF3 function. Here, we evaluated NR-Traf3 depletion effects on whole retinal TRAF3 protein expression, visual acuity, and retinal structure and function. Additionally, to determine if NR-Traf3 plays a role in retinal immune regulation, we used flow cytometry to assess immune cell infiltration following acute local lipopolysaccharide (LPS) administration. Our results show that TRAF3 protein is highly expressed in the NR and establish that NR-Traf3 depletion does not affect basal retinal structure or function. Importantly, NR-Traf3 promoted LPS-stimulated retinal immune infiltration. Thus, our findings propose NR-Traf3 as a positive regulator of retinal immunity. Further, the NR-Traf3 mouse provides a tool for investigations of neuronal TRAF3 as a novel potential target for therapeutic interventions aimed at suppressing retinal inflammatory disease and may also inform treatment approaches for inflammatory neurodegenerative brain conditions.
Cell Biology Life Sciences & Biomedicine Science & Technology

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