Synphilin-1 transgenic mice exhibit mild motor impairments.
Synphilin-1 represents a cytoplasmic protein that interacts with alpha-synuclein and localizes close to synaptic vesicles. The interaction of synphilin-1 with several proteins involved in Parkinson's disease suggests that it might be involved in the pathogenesis of the disease. Nonetheless, the function of synphilin-1 remains unclear. In the present study, we generated transgenic mice expressing human synphilin-1 under the prion protein promoter. Synphilin-1 was widely expressed in neurons in the brain including the substantia nigra, where massive loss of dopamine neurons was not observed. In the transgenic mouse brain, synphilin-1 protein was polyubiquitinated, and partially insoluble. Although modified-SHIRPA revealed no significant difference in behavior and morphology, the reduced rotarod performance and step length were observed in transgenic mice as compared with non-transgenic littermates. Synphilin-1 might be involved in motor function, and its accumulation in the central nervous system can cause motor impairments.
Jin
Hong-Guo
HG
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Hiroshima 734-8551, Japan.
Yamashita
Hiroshi
H
Nakamura
Takeshi
T
Fukuba
Hiromasa
H
Takahashi
Tetsuya
T
Hiji
Masanori
M
Kohriyama
Tatsuo
T
Matsumoto
Masayasu
M
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009069:Movement Disorders / Q000235:genetics* / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011930:Reaction Time / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C118958:SNCAIP protein, human; D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase