1. Late-onset olfactory deficits and mitral cell loss in mice lacking prion protein with ectopic expression of Doppel.
- Author
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Kim CK, Sakudo A, Taniuchi Y, Shigematsu K, Kang CB, Saeki K, Matsumoto Y, Sakaguchi S, Itohara S, and Onodera T
- Subjects
- Age of Onset, Aging physiology, Animals, Brain metabolism, Brain pathology, Caspase 3 metabolism, Cell Count, DNA, Single-Stranded metabolism, GPI-Linked Proteins, Gene Expression Regulation, Gliosis genetics, Gliosis pathology, Mice, Mice, Knockout, Olfaction Disorders pathology, Prion Proteins, Prions metabolism, Tissue Distribution, Olfaction Disorders genetics, Olfactory Bulb pathology, Prions genetics
- 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.
- Published
- 2007