NEURAL TUBE DEFECTS
神经管缺陷
基本信息
- 批准号:6659820
- 负责人:
- 金额:$ 103.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-09-01 至 2006-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (Provided by applicant): Neural tube defects (NTDs) occur in about
1/1000 births in the United States. Though much has been learned from these
defects, and folate treatment has significantly reduced their occurrence, much
remains to be learned. It has been estimated that perhaps 50% or more of all
NTDs have a genetic cause though the genes responsible generally are not
known. There is thought to be an influence of environmental effects on those
genetic deficits, but at what level is not known. This program project will
use several models to examine these questions with the goal of increasing
knowledge of the genetic component of NTDs. The project brings together six
investigators at Duke University who will work collaboratively on this
problem. The six projects include:
(1) John Klingensmith, who will study the basis of fully-penetrant NTD
phenotypes in mice mutant for the BMP antagonist noggin. He will misexpress
mutant BMP receptors via the Cre/lox system to determine how BMP signaling
controls dorsal development.
(2) Erik Meyers who will follow preliminary loss of function studies
indicating that a balance between the BMP and Fgf signaling families is
required for normal neural tube patterning and closure. Cre/loxP analysis will
ectopically localize either increased expression or decreased expression of
these components as a test of function.
(3) David McClay who will examine quantitative adhesion changes during normal
neural tube closure and compare those data with homozygotes having a fully
penetrant NTD and heterozygotes with no visible abnormal phenotype. The
hypothesis is that the heterozygotes will nevertheless have a measurable
deficit in adhesion.
(4) Dan Kiehart who will study dpp mutants (the BMP homolog in flies) that
cause a failure in dorsal closure. This process has many cellular
morphogenetic properties that are similar to neural tube closure in mammals.
He will screen for mutants in a search for genes whose products are required
for TGFbeta signaling function including cellular aspects of morphogenesis.
(5) Elwood Linney who will use a new promoter trap retroviral vector that his
laboratory constructed to identify and isolate genes expressed during neural
tube development in zebrafish.
(6) Marcy Speer, who, based on the other components of this PO1, will examine
the hereditary factors predisposing humans to NTDs, with the ultimate aim of
characterizing interactions between genes and between genes and the
environment, eventually leading to mechanisms for the prevention of these
frequent birth defects.
描述(由申请人提供):神经管缺陷(NTD)发生在约
1/1000出生在美国。尽管我们从这些事件中学到了很多
缺陷,叶酸治疗显着减少其发生,
还有待进一步研究。据估计,可能有50%或更多的
NTD有一个遗传原因,尽管负责的基因通常不是
知道的据认为,环境影响对这些人的影响是
遗传缺陷,但在什么水平上是未知的。该项目将
使用几个模型来检查这些问题,目的是增加
了解NTD的遗传成分。该项目汇集了六个
杜克大学的研究人员将在这方面进行合作
问题.这六个项目包括:
(1)John Klingensmith将研究全渗透NTD的基础
表型的小鼠突变体的BMP拮抗剂头蛋白。他会错误表达
突变BMP受体通过Cre/lox系统,以确定如何BMP信号转导
控制背部发育。
(2)Erik Meyers将跟踪初步的功能丧失研究
表明BMP和Fgf信号家族之间的平衡
正常神经管形成和闭合所需的能量Cre/loxP分析将
异位定位表达增加或表达减少
这些组件作为功能测试。
(3)大卫麦克雷,他将检查正常情况下的定量粘附变化,
神经管闭合,并将这些数据与具有完全
渗透NTD和杂合子,无可见异常表型。的
假设是杂合子仍然会有一个可测量的
附着力不足。
(4)Dan Kiehart将研究dpp突变体(苍蝇中的BMP同源物),
导致背侧闭合失败。这个过程有许多细胞
类似于哺乳动物神经管闭合的形态发生特性。
他将筛选突变体,以寻找其产物需要的基因。
TGF β信号传导功能,包括形态发生的细胞方面。
(5)埃尔伍德林尼将使用一种新的启动子陷阱逆转录病毒载体,
建立实验室,以鉴定和分离在神经元发育过程中表达的基因,
管发育在斑马鱼。
(6)Marcy Speer将根据PO 1的其他组成部分,
遗传因素使人类易患NTD,最终目的是
描述了基因之间的相互作用,
环境,最终导致预防这些机制
常见的出生缺陷
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)
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DAVID MCCLAY其他文献
DAVID MCCLAY的其他文献
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{{ truncateString('DAVID MCCLAY', 18)}}的其他基金
Transcriptional Casualty in Embryonic Morphogenesis: from the Specifications GRN
胚胎形态发生中的转录伤亡:来自 GRN 规范
- 批准号:
8092700 - 财政年份:2010
- 资助金额:
$ 103.36万 - 项目类别:
Sea Urchin Developmental Biology Conference XIV
第十四届海胆发育生物学会议
- 批准号:
6507470 - 财政年份:2002
- 资助金额:
$ 103.36万 - 项目类别:
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