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EXTRACELLULAR MATERIALS AND EMBRYONIC ORGAN FORMATION

EXTRACELLULAR MATERIALS AND EMBRYONIC ORGAN FORMATION
细胞外物质和胚胎器官的形成
批准号:
6520670
负责人:
MERTON R BERNFIELD
金额:
$3.23万
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
项目状态:
已结题
起止时间:
2000-03-01 至 2002-04-30

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中文摘要
翻译
描述(改编自研究人员摘要):Syndecans,细胞表面 硫酸乙酰肝素蛋白多糖(HSPG)结合并调节一个大的 细胞外效应器的数量。Syndecans的胞外结构域可以是 脱落,产生可以抑制这些细胞表面的可溶性HSPG 互动。几个表达高水平细胞的转基因小鼠品系 在CMV启动子/增强子的控制下产生表面Syndecan-1 评价其在体内的功能。Syndecan-1以多个 躯体组织和下丘脑中调节体重的区域。这个 转基因小鼠模拟(I)肥胖小鼠黑素皮质素-4异常 受体功能和(Ii)患有Bardet-Biedl综合征的人类,一种基因 病因不明的畸形和肥胖综合征。转基因表达的研究 Syndecan-1似乎已经发现了对摄食的生理控制 行为。 这些研究定义了Syndecans的新功能,并具有重要的 对理解饮食失调的启示,包括肥胖和恶病质。 肥胖是一个重大的公共健康危害;大约一半的美国女性和男性 现在被认为超重,国际移民组织表示,这一成本高于 美国每年700亿美元。因此,Syndecan归纳和Syndecan 相互作用可能是药物控制的重要新靶点 体重的影响。具体地说,调查人员的目标是探索 Syndecan-1过表达产生的表型:(I)确定 Syndecans与黑素皮质素受体相互作用的研究 并分析这种相互作用是如何进行的 在体外和体内调节黑素皮质素受体信号。(Ii) 评估下丘脑Syndecan-3的表达是否是生理性的 通过表征诱导性表达对摄食行为的调节 下丘脑Syndecan-3。分析syndecan-3基因缺失小鼠的摄食行为 确定下丘脑synce~an-3表达的潜在调节因子。(Iii) Syndecan-1的肥胖和形态发生异常分析 通过评估小鼠作为小鼠的遗传模型来过度表达小鼠 通过鉴定与Bardet-Biedl综合征相关的基因 形态发生异常,用于减轻肥胖。
英文摘要
DESCRIPTION (adapted from investigator's abstract): Syndecans, cell surface heparan sulfate proteoglycans, (HSPG) bind and modulate the activity of a large number of extra-cellular effectors. The ectodomains of the syndecans can be shed, generating soluble HSPGs that can inhibit these cell surface interactions. Several transgenic mouse lines that express high levels of cell surface syndecan- 1 under the control of a CMV promoter/enhancer were generated to evaluate its functions in vivo. Syndecan- 1 was expressed in multiple somatic tissues and in the hypothalamic areas that regulate body weight. The transgenic mice mimic (i) obese mice with abnormalities in melanocortin-4 receptor function and (ii) humans with the Bardet-Biedl syndrome, a genetic malformation and obesity syndrome of unknown etiology. Transgenic expression of syndecan- 1 appears to have has uncovered a physiological control of feeding behavior. These studies define new functions for syndecans and have important implications for understanding eating disorders, both obesity and cachexia. Obesity is a significant public health hazard; about half of U.S. women and men are now considered overweight and the IOM indicates that this costs more than $70 billion annually in the U.S. Thus, syndecan induction and syndecan interactions are potentially important new targets for pharmacological control of body weight. Specifically, the investigators aim to explore the remarkable phenotypes produced by syndecan- 1 overexpression: (i) establish the role of syndecans in melanocortin receptor function by characterizing the interaction of syndecans with agouti/AGRP peptides and analyzing how this interaction modulates melanocortin receptor signaling both in vitro and in vivo. (ii) evaluate whether hypothalamic expression of syndecan-3 is a physiological regulator of feeding behavior by characterizing the induced expression of hypothalamic syndecan-3. analyzing feeding behavior in syndecan-3 null mice and identifying potential regulators of hypothalamic synce~an-3 expression. (iii) analyze the obesity and morphogenetic abnormalities of the syndecan- 1 overexpressing mouse by evaluating the mouse as a genetic model of the Bardet-Biedl syndrome and by identifying the genes responsible for morphogenetic abnormalities and for reducing the obesity.
期刊论文(36)
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Heparin inhibits proliferation of fetal vascular smooth muscle cells in the absence of platelet-derived growth factor.
在缺乏血小板衍生生长因子的情况下,肝素可抑制胎儿血管平滑肌细胞的增殖。
DOI: 10.1002/jcp.1041270102
发表时间: 1986
期刊: Journal of cellular physiology
影响因子: 5.6
作者: [Benitz,WE, Lessler,DS, Coulson,JD, Bernfield,M]
通讯作者: Bernfield,M
Mesenchyme cells degrade epithelial basal lamina glycosaminoglycan.
间充质细胞降解上皮基底层糖胺聚糖。
DOI: 10.1016/0012-1606(82)90355-4
发表时间: 1982
期刊: Developmental biology
影响因子: 2.7
作者: [Smith,RL, Bernfield,M]
通讯作者: Bernfield,M
Possible regulation of FGF activity by syndecan, an integral membrane heparan sulfate proteoglycan.
Syndecan(一种完整膜硫酸乙酰肝素蛋白多糖)可能调节 FGF 活性。
DOI: 10.1111/j.1749-6632.1991.tb49029.x
发表时间: 1991
期刊: Annals of the New York Academy of Sciences
影响因子: 5.2
作者: [Bernfield,M, Hooper,KC]
通讯作者: Hooper,KC
DOI: 10.1083/jcb.105.6.3087
发表时间: 1987-12
期刊: The Journal of cell biology
影响因子: --
作者: [Jalkanen M, Rapraeger A, Saunders S, Bernfield M]
通讯作者: Bernfield M
共 26 条
    Syndecans: modulators of lung inflammation
    • 批准号:
      6655327
    • 项目类别:
    • 资助金额:
      $27.86万
    • 财政年份:
      2002
    • 负责人:
      MERTON R BERNFIELD
    • 依托单位:
    SYNDECANS AND SYNDECAN INDUCERS IN THE RESPONSE TO LUNG INJURY
    • 批准号:
      6410560
    • 项目类别:
    • 资助金额:
      $20.88万
    • 财政年份:
      2000
    • 负责人:
      MERTON R BERNFIELD
    • 依托单位:
    EXTRACELLULAR MATERIALS AND EMBRYONIC ORGAN FORMATION
    • 批准号:
      6363367
    • 项目类别:
    • 资助金额:
      $36.51万
    • 财政年份:
      2000
    • 负责人:
      MERTON R BERNFIELD
    • 依托单位:
    EXTRACELLULAR MATERIALS AND EMBRYONIC ORGAN FORMATION
    • 批准号:
      6054708
    • 项目类别:
    • 资助金额:
      $36.27万
    • 财政年份:
      2000
    • 负责人:
      MERTON R BERNFIELD
    • 依托单位:
    海外基金