title: CRBL cells: establishment, characterization and susceptibility to prion infection.
abstract: The cerebellum is involved in complex physiological functions including motor control, sensory perception, cognition, language, and emotion. Humans and animals with prion diseases are characterized clinically by ataxia, postural abnormalities and cognitive decline. Pathology in the cerebellum affected by prions includes spongiform degeneration, neuronal loss, and gliosis. To develop an in vitro model system for studying prion biology in cerebellar cells, we established and characterized an immortal cell line (CRBL) isolated from the cerebellum of mice lacking expression of a protein involved in cell cycle arrest. The characteristics of the cells include morphological heterogeneity, rapid proliferation, serum responsiveness during growth, and a change in the number of chromosomes. CRBL cells expressed both neuronal and glial cell markers as well as a considerable level of cellular prion protein, PrP(C). Upon in vitro infection, CRBL cells exhibited selective susceptibility to prions isolated from different sources. These cells chronically propagated prions from SMB cells. Strain-specific prion infection in CRBL cells was not due to instability of the cell line, allelic variance, or mutations in the PrP gene. Molecular properties of prions derived from SMB cells were maintained in the infected CRBL cells. Our results suggest that the specific interaction between a prion strain and hosts determined the selective susceptibility of CRBL cells, which reflects the conditions in vivo. In addition to the future studies revealing cellular and molecular mechanism involved in prion pathogenesis, CRBL cells will contribute to the studies dealing with prion strain properties and host susceptibilities.
authors.affiliation: Sanders Brown Center on Aging, Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose Street, HSRB-326, Lexington, KY 40536, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Mays
authors.forename: Hae-Eun
authors.initials: HE
authors.lastname: Kang
authors.forename: Younghwan
authors.initials: Y
authors.lastname: Kim
authors.forename: Sung Han
authors.initials: SH
authors.lastname: Shim
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Bang
authors.forename: Hee-Jong
authors.initials: HJ
authors.lastname: Woo
authors.forename: Youl-Hee
authors.initials: YH
authors.lastname: Cho
authors.forename: Jae-Beom
authors.initials: JB
authors.lastname: Kim
authors.forename: Chongsuk
authors.initials: C
authors.lastname: Ryou
mesh_terms: D000818:Animals; D002452:Cell Count; D002461:Cell Line, Transformed / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D003582:Cytogenetics / Q000379:methods; D004198:Disease Susceptibility; D005434:Flow Cytometry; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006031:Glycosylation; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D011328:Prions / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency
chemical_list: D005904:Glial Fibrillary Acidic Protein; D011328:Prions; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; C462941:beta3 tubulin, mouse