title: RML prions act through Mahogunin and Attractin-independent pathways.
abstract: While the conversion of the normal form of prion protein to a conformationally distinct pathogenic form is recognized to be the primary cause of prion disease, it is not clear how this leads to spongiform change, neuronal dysfunction and death. Mahogunin ring finger-1 (Mgrn1) and Attractin (Atrn) null mutant mice accumulate vacuoles throughout the brain that appear very similar to those associated with prion disease, but they do not accumulate the protease-resistant scrapie form of the prion protein or become sick. A study demonstrating an interaction between cytosolically-exposed prion protein and MGRN1 suggested that disruption of MGRN1 function may contribute to prion disease pathogenesis, but we recently showed that neither loss of MGRN1 nor MGRN1 overexpression influences the onset or progression of prion disease following intracerebral inoculation with Rocky Mountain Laboratory prions. Here, we show that loss of ATRN also has no effect on prion disease onset or progression and discuss possible mechanisms that could cause vacuolation of the central nervous system in Mgrn1 and Atrn null mutant mice and whether the same pathways might contribute to this intriguing phenotype in prion disease.
authors.affiliation: McLaughlin Research Institute; Great Falls, MT USA.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Gunn
authors.forename: George A
authors.initials: GA
authors.lastname: Carlson
mesh_terms: D000818:Animals; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C117928:Atrn protein, mouse; D008565:Membrane Proteins; D011328:Prions; C470689:Mgrn1 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: ATRN; Attractin; MGRN1; Mahogunin ring finger-1; PrP; prion disease; scrapie; spongiform encephalopathy; transmissible spongiform encephalopathy; vacuolation