PMID- 10499442 OWN - NLM STAT- MEDLINE DCOM- 19991007 LR - 20190513 IS - 0022-3069 (Print) IS - 0022-3069 (Linking) VI - 58 IP - 9 DP - 1999 Sep TI - PrPc glycoform heterogeneity as a function of brain region: implications for selective targeting of neurons by prion strains. PG - 1000-9 AB - We recently found that deletion of the Asn-linked carbohydrate (CHO) at residue 197 of Syrian hamster (SHa) PrP(C) while retaining the CHO at Asn 181 has a profound effect on which population of neurons are targeted for conversion of SHaPrP(C) to SHaPrP(Sc) in transgenic (Tg) mice inoculated with scrapie prions. We hypothesized that selective targeting of neuronal populations is determined by cell-specific differences in the affinity of an infecting PrP(Sc) (prion) for PrP(C) and that the affinity might be modulated by nerve cell-specific differences in PrP(C) glycosylation. Here we tested this hypothesis by assessing whether or not each brain region in Syrian hamsters synthesizes different PrP(C) glycoforms, as inferred from 2D-gel electrophoresis. Reproducible differences in the number and isoelectric point of PrP(C) charge isomers were found as a function of brain region. The results of this study support the hypothesis that the PrP(Sc) accumulation and the vacuolation pattern phenotypes in the brain are governed by neuron-specific differences in PrP(C) glycoforms. FAU - DeArmond, S J AU - DeArmond SJ AD - Department of Pathology, University of California, San Francisco 94143-0506, USA. FAU - Qiu, Y AU - Qiu Y FAU - Sanchez, H AU - Sanchez H FAU - Spilman, P R AU - Spilman PR FAU - Ninchak-Casey, A AU - Ninchak-Casey A FAU - Alonso, D AU - Alonso D FAU - Daggett, V AU - Daggett V LA - eng GR - AG02132/AG/NIA NIH HHS/United States GR - AG10770/AG/NIA NIH HHS/United States GR - NS14069/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - J Neuropathol Exp Neurol JT - Journal of neuropathology and experimental neurology JID - 2985192R RN - 0 (PrPC Proteins) RN - 0 (Prions) RN - 0 (Protein Isoforms) SB - IM MH - Animals MH - Brain/*metabolism MH - Cricetinae MH - Electrophoresis, Gel, Two-Dimensional MH - Isoelectric Point MH - Mesocricetus MH - Neurons/*virology MH - Osmolar Concentration MH - PrPC Proteins/chemistry/*metabolism MH - Prions/genetics/*physiology MH - Protein Isoforms/chemistry/metabolism MH - Tissue Distribution EDAT- 1999/09/28 00:00 MHDA- 1999/09/28 00:01 CRDT- 1999/09/28 00:00 PHST- 1999/09/28 00:00 [pubmed] PHST- 1999/09/28 00:01 [medline] PHST- 1999/09/28 00:00 [entrez] AID - 10.1097/00005072-199909000-00010 [doi] PST - ppublish SO - J Neuropathol Exp Neurol. 1999 Sep;58(9):1000-9. doi: 10.1097/00005072-199909000-00010.