title: Late-onset olfactory deficits and mitral cell loss in mice lacking prion protein with ectopic expression of Doppel.
abstract: Several lines of prion protein gene (Prnp)-knockout mice such as ZrchI, ZrchII, Npu, Ngsk and Rcm0 have been generated. Of these, ZrchII, Ngsk and Rcm0 exhibit late-onset ataxia due to ectopic expression of Doppel (Dpl); a result of damage to the splicing acceptor of Prnp exon 3. Recently, we developed another line of Prnp-/- mice (Rikn), which was generated by gene targeting with more nucleotides by replacing intron 2 with the pgk-neo gene (cf. Ngsk Prnp-/- mice) and showed not only ataxia but also a lower olfactory sensitivity than the other Prnp-/- mouse line ZrchI at over 60 weeks of age. The histopathology of the elderly Rikn Prnp-/- mice showed mitral cell loss concomitantly observed with gliosis of astrocytes. Western blot analysis showed that Dpl was detected in the cerebrum, cerebellum and olfactory bulb of Rikn Prnp-/- mice, where aberrant histopathology was observed. Thus, mitral cell loss and gliosis induced by ectopic Dpl expression were probably associated with the late-onset olfactory deficits in Rikn Prnp-/- mice.
authors.affiliation: Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Chi-Kyeong
authors.initials: CK
authors.lastname: Kim
authors.forename: Akikazu
authors.initials: A
authors.lastname: Sakudo
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Taniuchi
authors.forename: Kazuto
authors.initials: K
authors.lastname: Shigematsu
authors.forename: Chung-Boo
authors.initials: CB
authors.lastname: Kang
authors.forename: Keiichi
authors.initials: K
authors.lastname: Saeki
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Suehiro
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Takashi
authors.initials: T
authors.lastname: Onodera
mesh_terms: D017668:Age of Onset; D000375:Aging / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D004277:DNA, Single-Stranded / Q000378:metabolism; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D005911:Gliosis / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D000857:Olfaction Disorders / Q000235:genetics* / Q000473:pathology; D009830:Olfactory Bulb / Q000473:pathology*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D004277:DNA, Single-Stranded; D058851:GPI-Linked Proteins; D000072002:Prion Proteins; D011328:Prions; C122036:Prnd protein, mouse; C512657:Prnp protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3