Late-onset olfactory deficits and mitral cell loss in mice lacking prion protein with ectopic expression of Doppel.
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.
Kim
Chi-Kyeong
CK
Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
Sakudo
Akikazu
A
Taniuchi
Yojiro
Y
Shigematsu
Kazuto
K
Kang
Chung-Boo
CB
Saeki
Keiichi
K
Matsumoto
Yoshitsugu
Y
Sakaguchi
Suehiro
S
Itohara
Shigeyoshi
S
Onodera
Takashi
T
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
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