PURINE, FOLATE, AND REACTIVE OXYGEN METABOLISM AND DOWN SYNDROME
嘌呤、叶酸和活性氧代谢与唐氏综合症
基本信息
- 批准号:6301897
- 负责人:
- 金额:$ 17.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-01-01 至 2000-12-31
- 项目状态:已结题
- 来源:
- 关键词:Downs syndrome adenosine triphosphate brain mapping chromosome 21 diploidy disease /disorder model enzyme activity enzyme deficiency folate free radical oxygen gene expression gene mutation gene targeting genetically modified animals human tissue hydroxymethyltransferases laboratory mouse miscellaneous oxidoreductase phenotype polymerase chain reaction purine /pyrimidine metabolism purines trisomy urate vitamin metabolism
项目摘要
This component investigates the hypothesis that metabolic abnormalities
due to increased dosages of specific enzymes may cause some of the
phenotypes seen in Down Syndrome, especially those affecting
neurocognitive and sensorineural development and neurodegeneration.
Chromosome 21 genes involved in the interrelated pathways of purine,
folate, and reactive oxygen species (ROS) metabolism will be examine,
because mutations in all these pathway lead to neurological deficits in
humans. Transgenic and knockout mice altered to the purine and Ros
pathways have developmental anomalies, including neurological deficits,
consistent with the expected effects of alteration of the pathways and
also consistent with the human phenotypes seen in individuals with
mutations in the pathways. Transgenic mice expressing genes in the purine
pathways have been obtained during the current funding period. Specific
aims include: 1) characterization of the phenotypes of the transgenic mice
already obtained; 2) creation of additional transgenic mice expressing the
human ATP50 gene encoding a subunit of ATP synthase and the human gene for
carbonyl reductase and analysis of these mice; 3) creation of Ts65Dn-
uricase deficient partial trisomy 16 mouse to serve as a higher fidelity
mouse model of human metabolism; 4) crossing the mice created in 4 with
the reduced folate carrier transgenic mice and analysis of the effect of
this on the phenotype of the Ts65Dn mouse; 5) creation and analysis of
knockout mice for four of the genes (GART, ATP50, CBR, and SOD1) in the
region trisomeric in the Ts65Dn mouse and appropriate breeding of these to
determine the effect of restoring these genes to the normal diploid state;
6) analysis of the expression of the genes under study in brain samples
from individuals with and without Down Syndrome; and 7) assessment of the
role of urate on ROS metabolism by appropriate crosses of mice with
alterations in the ROS pathway and the uricase deficient mice. These
experiments should result in a rigorous understanding of the role of these
pathways in cognition and neural development and whether trisomy of the
genes in the pathway plays a role in DS.
该组件研究代谢异常的假设
由于增加特定酶的剂量可能会导致一些
唐氏综合征的表型,尤其是那些影响
神经认知和感觉神经发育和神经退化。
21号染色体上的基因参与了嘌呤的相互联系的途径,
将检查叶酸和活性氧(ROS)代谢,
因为所有这些途径的突变都会导致神经功能障碍
人类。转基因和基因敲除小鼠改变为嘌呤和ROS
通路有发育异常,包括神经缺陷,
与路径改变的预期效果和
也与人类的表型一致,在患有
这些途径中的突变。在嘌呤中表达基因的转基因小鼠
在本供资期间已经获得了途径。特定的
目的包括:1)转基因小鼠的表型特征
已获得;2)创建更多表达该基因的转基因小鼠
编码三磷酸腺苷合成酶亚基的人ATP50基因和
3)Ts65Dn-Ts65的构建
尿酸酶缺陷型部分三体16小鼠作为保真度较高的小鼠
人类新陈代谢的小鼠模型;4)将4年中创建的小鼠与
还原型叶酸载体转基因小鼠及其干预效果分析
这是关于Ts65Dn小鼠的表型;5)创造和分析
中的四个基因(GART、ATP50、CBR和SOD1)被敲除的小鼠
Ts65Dn小鼠的区域三聚体及其选育
确定将这些基因恢复到正常二倍体状态的效果;
6)分析正在研究的基因在大脑样本中的表达
来自患有和不患有唐氏综合症的个人;以及7)评估
尿酸对小鼠适当杂交后ROS代谢的影响
ROS途径和尿酸酶缺陷小鼠的变化。这些
实验应该导致对这些因素的作用有一个严格的理解
认知和神经发育的途径以及三体是否
该途径中的基因在DS中起着作用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
DAVID PATTERSON其他文献
DAVID PATTERSON的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('DAVID PATTERSON', 18)}}的其他基金
Proteomics for Testing Hypotheses about Down Syndrome
用于检验唐氏综合症假设的蛋白质组学
- 批准号:
7248057 - 财政年份:2004
- 资助金额:
$ 17.74万 - 项目类别:
Proteomics for Testing Hypotheses about Down Syndrome
用于检验唐氏综合症假设的蛋白质组学
- 批准号:
6926190 - 财政年份:2004
- 资助金额:
$ 17.74万 - 项目类别:
Proteomics for Testing Hypotheses about Down Syndrome
用于检验唐氏综合症假设的蛋白质组学
- 批准号:
7082872 - 财政年份:2004
- 资助金额:
$ 17.74万 - 项目类别:
Proteomics for Testing Hypotheses about Down Syndrome
用于检验唐氏综合症假设的蛋白质组学
- 批准号:
6826136 - 财政年份:2004
- 资助金额:
$ 17.74万 - 项目类别:
AUTISM AND AMPS LYASE MUTATIONS: CELL AND MOUSE MODELS
自闭症和 AMPS 裂解酶突变:细胞和小鼠模型
- 批准号:
6579811 - 财政年份:2003
- 资助金额:
$ 17.74万 - 项目类别:
AUTISM AND AMPS LYASE MUTATIONS: CELL AND MOUSE MODELS
自闭症和 AMPS 裂解酶突变:细胞和小鼠模型
- 批准号:
6868232 - 财政年份:2003
- 资助金额:
$ 17.74万 - 项目类别:
AUTISM AND AMPS LYASE MUTATIONS: CELL AND MOUSE MODELS
自闭症和 AMPS 裂解酶突变:细胞和小鼠模型
- 批准号:
6703721 - 财政年份:2003
- 资助金额:
$ 17.74万 - 项目类别:
AUTISM AND AMPS LYASE MUTATIONS: CELL AND MOUSE MODELS
自闭症和 AMPS 裂解酶突变:细胞和小鼠模型
- 批准号:
7172954 - 财政年份:2003
- 资助金额:
$ 17.74万 - 项目类别:
AUTISM AND AMPS LYASE MUTATIONS: CELL AND MOUSE MODELS
自闭症和 AMPS 裂解酶突变:细胞和小鼠模型
- 批准号:
7012827 - 财政年份:2003
- 资助金额:
$ 17.74万 - 项目类别:
CONFERENCE--NEW DIRECTIONS IN DOWN SYNDROME RESEARCH
会议——唐氏综合症研究的新方向
- 批准号:
6190811 - 财政年份:2000
- 资助金额:
$ 17.74万 - 项目类别:
相似海外基金
Adenosine triphosphate as a master variable for biomass in the oceanographic context
三磷酸腺苷作为海洋学背景下生物量的主变量
- 批准号:
2319114 - 财政年份:2023
- 资助金额:
$ 17.74万 - 项目类别:
Standard Grant
Characterizing the Interaction Between Adenosine Triphosphate and Pathological Alpha-synuclein Structures in Parkinson's Disease
表征帕金森病中三磷酸腺苷与病理性 α-突触核蛋白结构之间的相互作用
- 批准号:
565727-2021 - 财政年份:2021
- 资助金额:
$ 17.74万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Master's
Investigation of the development of pain during orthodontic tooth movement with adenosine triphosphate
三磷酸腺苷正畸牙齿移动过程中疼痛发生的研究
- 批准号:
20K18789 - 财政年份:2020
- 资助金额:
$ 17.74万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Neural Regulation of Adenosine Triphosphate (ATP) in the Nasal Mucosa
鼻粘膜三磷酸腺苷 (ATP) 的神经调节
- 批准号:
19K18793 - 财政年份:2019
- 资助金额:
$ 17.74万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Dynamics of the oxygen-dependent release of adenosine triphosphate from erythrocytes
红细胞氧依赖性三磷酸腺苷释放的动力学
- 批准号:
460605-2014 - 财政年份:2016
- 资助金额:
$ 17.74万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Development of an Analytical Tool Utilizing Electrochemical Detection Methods For the Measuring of Protein Kinase Activity on a Protein Substrate Using Ferrocene-Adenosine Triphosphate (Fc-ATP) as a C
利用电化学检测方法开发分析工具,以二茂铁-三磷酸腺苷 (Fc-ATP) 作为 C,测量蛋白质底物上的蛋白激酶活性
- 批准号:
469948-2014 - 财政年份:2016
- 资助金额:
$ 17.74万 - 项目类别:
Vanier Canada Graduate Scholarship Tri-Council - Doctoral 3 years
Adenosine Triphosphate as a Signal for Evaluating Microbial Risk from Groundwater Supplies
三磷酸腺苷作为评估地下水供应微生物风险的信号
- 批准号:
507411-2016 - 财政年份:2016
- 资助金额:
$ 17.74万 - 项目类别:
Engage Grants Program
Development of an Analytical Tool Utilizing Electrochemical Detection Methods For the Measuring of Protein Kinase Activity on a Protein Substrate Using Ferrocene-Adenosine Triphosphate (Fc-ATP) as a C
利用电化学检测方法开发分析工具,以二茂铁-三磷酸腺苷 (Fc-ATP) 作为 C,测量蛋白质底物上的蛋白激酶活性
- 批准号:
469948-2014 - 财政年份:2015
- 资助金额:
$ 17.74万 - 项目类别:
Vanier Canada Graduate Scholarship Tri-Council - Doctoral 3 years
Dynamics of the oxygen-dependent release of adenosine triphosphate from erythrocytes
红细胞氧依赖性三磷酸腺苷释放的动力学
- 批准号:
460605-2014 - 财政年份:2015
- 资助金额:
$ 17.74万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Dynamics of the oxygen-dependent release of adenosine triphosphate from erythrocytes
红细胞氧依赖性三磷酸腺苷释放的动力学
- 批准号:
460605-2014 - 财政年份:2014
- 资助金额:
$ 17.74万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral