Heritable disorder resembling neuronal storage disease in mice expressing prion protein with deletion of an α-helix
- 1 July 1997
- journal article
- research article
- Published by Springer Nature in Nature Medicine
- Vol. 3 (7) , 750-755
- https://doi.org/10.1038/nm0797-750
Abstract
Mice were constructed carrying prion protein (PrP) transgenes with individual regions of putative secondary structure deleted. Transgenic mice with amino-terminal regions deleted remained healthy at >400 days of age, whereas those with either of carboxy-terminal α-helices deleted spontaneously developed fatal CNS illnesses similar to neuronal storage diseases. Deletion of either C-terminal helix resulted in PrP accumulation within cytoplasmic inclusions in enlarged neurons. Deletion of the penultimate C-terminal helix resulted in proliferation of rough endoplasmic reticulum. Mice with the C-terminal helix deleted were affected with nerve cell loss in the hippocampus and proliferation of smooth endoplasmic reticulum. Whether children with the human counterpart of this malady will be found remains to be determined.Keywords
This publication has 37 references indexed in Scilit:
- NMR structure of the mouse prion protein domain PrP(121–231)Nature, 1996
- Ecdysone-inducible gene expression in mammalian cells and transgenic mice.Proceedings of the National Academy of Sciences, 1996
- High-Level Expression and Characterization of a Purified 142-Residue Polypeptide of the Prion ProteinBiochemistry, 1996
- Conformational Transformations in Peptides Containing Two Putative α-Helices of the Prion ProteinJournal of Molecular Biology, 1995
- Epidemiology of Creutzfeldt-Jakob Disease in the United States, 1979–1990: Analysis of National Mortality DataNeuroepidemiology, 1995
- Fatal Familial Insomnia and Familial Creutzfeldt‐Jakob Disease: Clinical, Pathological and Molecular FeaturesBrain Pathology, 1995
- Prion Protein Gene Variation Among PrimatesJournal of Molecular Biology, 1995
- Intracellular accumulation of the cellular prion protein after mutagenesis of its Asnlinked glycosylation sitesGlycobiology, 1990
- Control Of Protein Exit From The Endoplasmic ReticulumAnnual Review of Cell and Developmental Biology, 1989
- A C-terminal signal prevents secretion of luminal ER proteinsPublished by Elsevier ,1987