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Updated: Jul 4, 2026
Bioluminescence Imaging of Neuroinflammation in Transgenic Mice After Peripheral Inoculation of Alpha-Synuclein Fibrils
Published on: April 13, 2017
GFP-tagged mutant prion protein forms intra-axonal aggregates in transgenic mice
Andrea Z Medrano1, Sami J Barmada, Emiliano Biasini
1Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Abstract:
A nine-octapeptide insertional mutation in the prion protein (PrP) causes a fatal neurodegenerative disorder in both humans and transgenic mice. To determine the precise cellular localization of this mutant PrP (designated PG14), we have generated transgenic mice expressing PG14-EGFP, a fluorescent fusion protein that can be directly visualized in vivo. Tg(PG14-EGFP) mice develop an ataxic neurological illness characterized by astrogliosis, PrP aggregation, and accumulation of a partially protease-resistant form of the mutant PrP. Strikingly, PG14-EGFP forms numerous fluorescent aggregates in the neuropil and white matter of multiple brain regions. These aggregates are particularly prominent along axonal tracts in both brain and peripheral nerve, and similar intracellular deposits are visible along the processes of cultured neurons. Our results reveal intra-axonal aggregates of a mutant PrP, which could contribute to the pathogenesis of familial prion disease by disrupting axonal transport.
Insights
A mutation in prion protein (PrP) causes neurodegeneration. Researchers found this mutant PrP forms aggregates within axons, potentially disrupting transport and contributing to familial prion disease.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Familial prion diseases are fatal neurodegenerative disorders.
- A nine-octapeptide insertional mutation in prion protein (PrP) is linked to these conditions.
- The precise cellular localization of this mutant PrP, termed PG14, was previously unknown.
Purpose of the Study:
- To determine the cellular localization of the mutant prion protein (PG14).
- To investigate the in vivo formation and distribution of PG14 aggregates.
Main Methods:
- Generation of transgenic mice expressing PG14 fused to EGFP (PG14-EGFP).
- In vivo visualization of the fluorescent fusion protein.
- Analysis of neurological symptoms, including astrogliosis and PrP aggregation.
Main Results:
- PG14-EGFP mice exhibited an ataxic neurological illness.
- Fluorescent PG14-EGFP aggregates were observed in the neuropil and white matter.
- Aggregates were prominently located along axonal tracts in both central and peripheral nervous systems.
- Intracellular deposits were also visible along neuronal processes in cultured neurons.
Conclusions:
- Mutant PrP (PG14) forms intra-axonal aggregates.
- These intra-axonal aggregates may contribute to familial prion disease pathogenesis.
- Disruption of axonal transport is a potential mechanism underlying the observed neurodegeneration.
