STAGE SPECIFIC EMBRYONIC ANTIGEN-1 GLYCOCONJUGATES IN DEVELOPING RAT CEREBELLUM
大鼠小脑发育阶段特异性胚胎抗原-1 糖复合物
基本信息
- 批准号:6271949
- 负责人:
- 金额:$ 11.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-12-01 至 1998-11-30
- 项目状态:已结题
- 来源:
- 关键词:adeno associated virus group cerebellum developmental neurobiology embryo /fetus antigen embryo /fetus cell /tissue enzyme activity fucose genetic promoter element glycolipids glycoprotein biosynthesis glycoproteins glycosphingolipids hexosyltransferase immunocytochemistry in situ hybridization laboratory rat lipid biosynthesis newborn animals northern blottings polymerase chain reaction
项目摘要
Evidence that fucosylated glycoconjugates play a significant role in
brain development is suggested by reports of severe mental retardation
in patients that lack fucose residues. However, the mechanisms by which
fucosylated glycoconjugates influence brain development are not known.
The epitope 3-fucosyl-N-acetylactosamine (SSEA-1) is an excellent
candidate to play a vital role in brain development, both because it is
expressed in developing brain with temporal and spatial specificity, and
because it has been shown to have a key role in cell-cell interactions
in other tissues. Thus, we postulate that SSEA-1 plays a key role in the
cell-cell interactions required for normal neural development. Our
preliminary results indicate that SSEA-1 glycolipid expression in
neonatal cerebellum correlates with granule cell migration, and the goal
of this project is to elucidate the role of these molecules in this
process. Specifically, we will characterize and measure SSEA-1
glycosphingolipids and proteins in developing rat cerebellum and relate
these data to the stage and regional immunohistochemical appearance of
this antigen. We also will characterize the fucosyltransferase
activities involved in SSEA-1 glycoconjugate synthesis during cerebellar
development, as our data suggests fucosyltransferase(s) play a critical
role in controlling SSEA-1 glycolipid expression. Simultaneously, we
will characterize the genes responsible for these fucosyltransferase
activities and evaluate their regulation during development. Results
obtained from these studies will then enable us to investigate the
biological role of SSEA-1 glycoconjugates. We propose to determine
whether overexpression, or blocking the accessibility, of SSEA-1 antigens
in the neonatal cerebellum would result in anomalous behavior of
developing granule cells. To cause over expression of SSEA-1, we propose
to inject intracerebrally neonatal rats with AAV vectors carrying an
epitope-tagged form of the relevant cloned rat fucosyltransferase under
the control of a strong non-tissue specific promoter. To block the
function of SSEA-1, we plan to inject irradiated hybridoma cells
producing anti-SSEA-1 antibodies. These brains will then be examined
histologically during subsequent development to establish the degree of
fucosyltransferase and SSEA-1 expression and to determine whether
perturbing SSEA-1 expression or availability changes the normal pattern
of granule cell migration, parallel fiber extension and/or
synaptogenesis.
证据表明,集中的糖缀合物在
项目成果
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{{ truncateString('ROBERT H MC CLUER', 18)}}的其他基金
STAGE SPECIFIC EMBRYONIC ANTIGEN-1 GLYCOCONJUGATES IN DEVELOPING RAT CEREBELLUM
大鼠小脑发育阶段特异性胚胎抗原-1 糖复合物
- 批准号:
6301842 - 财政年份:1999
- 资助金额:
$ 11.45万 - 项目类别:
STAGE SPECIFIC EMBRYONIC ANTIGEN-1 GLYCOCONJUGATES IN DEVELOPING RAT CEREBELLUM
大鼠小脑发育阶段特异性胚胎抗原-1 糖复合物
- 批准号:
6108184 - 财政年份:1998
- 资助金额:
$ 11.45万 - 项目类别:
STAGE SPECIFIC EMBRYONIC ANTIGEN-1 GLYCOCONJUGATES IN DEVELOPING RAT CEREBELLUM
大鼠小脑发育阶段特异性胚胎抗原-1 糖复合物
- 批准号:
6240771 - 财政年份:1996
- 资助金额:
$ 11.45万 - 项目类别:
MINORITY HIGH SCHOOL STUDENT RESEARCH APPRENTICE PROGRAM
少数民族高中生研究学徒计划
- 批准号:
2282554 - 财政年份:1986
- 资助金额:
$ 11.45万 - 项目类别:
MINORITY HIGH SCHOOL STUDENT RESEARCH APPRENTICE PROGRAM
少数民族高中生研究学徒计划
- 批准号:
3512564 - 财政年份:1986
- 资助金额:
$ 11.45万 - 项目类别:
MINORITY HIGH SCHOOL STUDENT RESEARCH APPRENTICE PROGRAM
少数民族高中生研究学徒计划
- 批准号:
3512563 - 财政年份:1986
- 资助金额:
$ 11.45万 - 项目类别:
MINORITY HIGH SCHOOL STUDENT RESEARCH APPRENTICE PROGRAM
少数民族高中生研究学徒计划
- 批准号:
3512562 - 财政年份:1986
- 资助金额:
$ 11.45万 - 项目类别:
EKS CENTER REQUEST FOR VG MM707E MS WITH LC INTERFACE
EKS 中心要求配备 LC 接口的 VG MM707E MS
- 批准号:
3519233 - 财政年份:1985
- 资助金额:
$ 11.45万 - 项目类别:
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