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Published on: April 13, 2017
Extraneural manifestations of prion infection in GPI-anchorless transgenic mice
Andrew M Lee1, Johan F Paulsson, Justin Cruite
1Viral Immunobiology Laboratory, Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA. andrewl@scripps.edu
Abstract:
Earlier studies indicated that transgenic (tg) mice engineered to express prion protein (PrP) lacking the glycophosphatidylinositol (GPI⁻/⁻) membrane anchor formed abnormal proteinase-resistant prion (PrPsc) amyloid deposits in their brains and hearts when infected with the RML strain of murine scrapie. In contrast, RML scrapie infection of normal mice with a GPI-anchored PrP did not deposit amyloid with PrPsc in the brain or the heart. Here we report that scrapie-infected GPI⁻/⁻ PrP tg mice also deposit PrP and transmissible infectious material in the gut, kidneys, and islets of Langerhans. Similar to previously reported amyloid deposits in the brain and heart, amyloid deposits were found in the gut; however, no amyloid deposited in the islets. By high-resolution electron microscopy, we show PrP is located primarily in α cells and also β cells. Islets contain abundant insulin and there is no abnormality in glucose metabolism in infected GPI⁻/⁻ PrP tg mice.
Insights
Transgenic mice lacking prion protein (PrP) anchors deposit PrP in organs like the gut and kidneys after scrapie infection. These mice show no amyloid in islets of Langerhans, despite PrP presence in alpha and beta cells.
Area of Science:
- Neuroscience
- Pathology
- Molecular Biology
Background:
- Transgenic mice expressing prion protein (PrP) without a GPI anchor develop PrPsc amyloid in the brain and heart after RML scrapie infection.
- Normal mice with GPI-anchored PrP do not form PrPsc amyloid deposits in the brain or heart when infected with RML scrapie.
Purpose of the Study:
- To investigate the distribution of PrP deposits and infectious material in scrapie-infected transgenic mice lacking the GPI anchor for PrP.
- To examine the presence of amyloid deposits in additional organs, including the gut, kidneys, and islets of Langerhans.
Main Methods:
- Scrapie infection of transgenic (tg) mice engineered to express prion protein (PrP) lacking the glycophosphatidylinositol (GPI) membrane anchor.
- Analysis of PrP and PrPsc deposition in various organs using histological and biochemical methods.
- High-resolution electron microscopy to examine PrP localization within the islets of Langerhans.
Main Results:
- Scrapie-infected GPI⁻/⁻ PrP tg mice deposit PrP and infectious material in the gut, kidneys, and islets of Langerhans.
- Amyloid deposits are found in the gut, mirroring findings in the brain and heart.
- No amyloid deposits are observed in the islets, although PrP is localized in alpha and beta cells; glucose metabolism remains normal.
Conclusions:
- Prion protein deposition in scrapie-infected mice lacking the GPI anchor extends beyond the brain and heart to the gut and kidneys.
- The absence of amyloid in islets, despite PrP presence, suggests organ-specific mechanisms influencing amyloid formation.
- Normal glucose metabolism in infected islets indicates that PrP deposition in this tissue does not immediately impair function.
