NR AYHI
AU Kim,C.K.; Sakudo,A.; Taniuchi,Y.; Shigematsu,K.; Kang,C.B.; Saeki,K.; Matsumoto,Y.; Sakaguchi,S.; Itohara,S.; Onodera,T.
TI Late-onset olfactory deficits and mitral cell loss in mice lacking prion protein with ectopic expression of Doppel
QU International Journal of Molecular Medicine 2007 Aug; 20(2): 169-76
PT journal article; research support, non-u.s. gov't
AB 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.
MH Age of Onset; Aging/physiology; Animals; Brain/metabolism/pathology; Caspase 3/metabolism; Cell Count; DNA, Single-Stranded/metabolism; Gene Expression Regulation; Gliosis/genetics/pathology; Mice; Mice, Knockout; Olfaction Disorders/*genetics/pathology; Olfactory Bulb/*pathology; Prions/*genetics/metabolism; Tissue Distribution
AD Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
SP englisch
PO Griechenland