1989 Fiscal Year Final Research Report Summary
Analysis of pathogenetic mechanism of Alzheimer's disease using trisomy 16 chimera mice
| Project/Area Number |
63570375
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | National Center of Neurology and Psychiatry (NCNP) |
|---|
Principal Investigator |
NISHIZAWA Masatoyo Natl.Inst.Neurosci., NCNP, Section Chief, 神経研究所・疾病研究第6部, 室長 (80198457)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAMEGAI Masahiro Natl.Inst.Neurosci., NCNP, Section Chief, 神経研究所・疾病研究第6部, 研究員
KUNISHITA Tatsuhide Natl.Inst.Neurosci., NCNP, Section Chief, 神経研究所・疾病研究第6部, 室長 (40167383)
TAKAHASHI Keikichi Natl.Inst.Neurosci., NCNP, Section Chief, 神経研究所・疾病研究第6部, 室長 (40117148)
TABIRA Takeshi Natl.Inst.Neurosci., NCNP, Section Chief, 神経研究所・疾病研究第6部, 部長 (80112332)
HANAOKA Kazunori Natl.Inst.Neurosci., NCNP, Section Chief, 神経研究所・モデル動物開発部, 室長 (40189577)
|
|---|
| Project Period (FY) |
1988 – 1989
|
| Keywords | Trisomy 16 mouse / Alzheimer's disease / Down syndrome / Animal model / Chimera mouse |
|---|
| Research Abstract |
Trisomy 16 mice (Ts16) have been considered as an animal model for human trisomy 21 (Down syndrome). The object of this study is to examine whether Ts16 can also be a useful experimental system for analyzing the mechanism of beta amyloid protein deposition in Alzheimer's disease (AD), because the gene encoding amyloid precursor protein was found to be located on mouse chromosome 16. For this purpose, we have to rescue cells of the Ts16 central nervous system (CNS) using the following methods, since most, if not all, of the Ts16 cannot survive after birth. First, we have established a system to produce Ts16 2n chimera mice using the aggregation method. The chimeric mice so far obtained do not show any behaviological abnormalities until 1 year after birth. Second, Ts16 fetal CNS tissues have been transplanted into normal adult mouse brains. Detailed histological analyses. are necessary to see whether beta amyloid is actually deposited in the brains of these mice. Third, a primary culture system for fetal CNS neurons has been established. We have found that in Ts16 basal forebrain cholinergic neurons choline acetyltransferase activity cannot be induced by exogenousely added nerve growth factor (NGF). and that NGF content is increased in Ts16 fetal brains. These results will give clues to study the mechanism of cholinergic dysfunction in AD.
|
