Use of a phosphosensor dye in proteomic analysis of human mutant tau transgenic mice.
Recently, we have generated transgenic mice (designated as SJLB) carrying human N279K mutant tau, one of the tau mutations causing parkinsonism linked to chromosome 17 (FTDP-17). SJLB mice mimic some features of behavioral alterations and neuronal pathology of patients with Alzheimer's disease. To investigate how tau dysfunctions cause these features, we examined the expression and phosphorylation levels in SJLB mouse hippocampal proteins using a phosphosensor dye in two-dimensional poly acrylamide gel electrophoresis analysis and mass spectrometry. Calreticulin and tubulin beta4 are significantly more phosphorylated, and heat shock cognate 71 kDa protein, tubulin beta2, vacuolar ATP synthase catalytic subunit A, alpha-internexin, alpha-enolase, ubiquitin carboxyl-terminal hydrolase isozyme L1, and complexin-2 are significantly less phosphorylated in SJLB mice than control mice. These proteins could be new targets for elucidating underlying mechanisms and therapeutic intervention in neurodegenerative diseases.
Takano
Masaoki
M
Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji 670-8524, Japan.
Otani
Mieko
M
Sakai
Akiko
A
Kadoyama
Keiichi
K
Matsuyama
Shogo
S
Matsumoto
Akira
A
Takenokuchi
Mariko
M
Sumida
Miho
M
Taniguchi
Taizo
T
D000818:Animals; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005456:Fluorescent Dyes; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020125:Mutation, Missense; D010766:Phosphorylation; D040901:Proteomics / Q000379:methods*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D005456:Fluorescent Dyes; C054369:MAPT protein, human; D016875:tau Proteins