POSITIONAL CLONING OF THE MEN1 GENE
MEN1 基因的定位克隆
基本信息
- 批准号:6988572
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:Drosophilidaebiotechnologycell differentiationcell growth regulationcell lineembryonic stem cellgene mutationgenetic mappinggenetic markersgenetically modified animalshematopoietic stem cellshuman genetic material taglaboratory mousemolecular cloningmultiple endocrine neoplasianeoplasm /cancer geneticsnuclear proteinspancreatic islet neoplasmparathyroid neoplasmspituitary neoplasmstranscription factor
项目摘要
Multiple endocrine neoplasia type 1 (MEN1) is characterized by multiple
tumors of the parathyroid, anterior pituitary and GI endocrine tissues.
We have shown earlier that mutations in the MEN1 gene are responsible
for the MEN1 syndrome. The MEN1 encoded nuclear protein, Menin,
binds the transcription factors JunD and NFkB, and can repress JunD and
NFkB-induced transcription. By expressing WT or mutant JunD in mouse fibroblast cell lines that are null for menin and JunD, we find that interaction with menin is required for the growth suppressor function(s) of JunD. We have developed both conventional and
conditional mouse knockout models, which yield phenotypes that are
remarkably similar to the human MEN1 disease, and have allowed us to
delineate the stages in tumor development. In addition, we have
developed tissue specific menin-inducible transgenic mouse models.
Expression changes associated with presence or absence of menin in cell lines and during tumorigenesis, and specifically identification of the promoters of the genes with which menin is associated, are being studied to understand the biology of menin. The role of menin in differentiation of ES cells to pancreatic islet and hematopoietic lineages is being explored. In addition, tissue specific transgenic expression and knockout models for MEN1 are being developed in Drosophila. These models should help to understand the functional role(s) of menin and suggest possible therapeutic directions.
多发性内分泌瘤1型(MEN1)的特征是多个
甲状旁腺、垂体前叶和胃肠道内分泌组织的肿瘤。
我们之前已经证明MEN1基因的突变是导致
MEN1综合征MEN1编码的核蛋白Menin,
结合转录因子JunD和NF κ B,并可抑制JunD,
NF κ B诱导的转录。通过在对menin和JunD无效的小鼠成纤维细胞系中表达WT或突变型JunD,我们发现与menin的相互作用是JunD的生长抑制功能所必需的。我们开发了传统的和
条件性小鼠基因敲除模型,其产生的表型
与人类MEN1疾病非常相似,并使我们能够
描绘肿瘤发展的阶段。另外我们有
开发了组织特异性脑膜炎诱导型转基因小鼠模型。
与menin在细胞系和肿瘤发生过程中的存在或不存在相关的表达变化,以及与menin相关的基因的启动子的具体鉴定,正在研究以了解menin的生物学。menin在ES细胞分化为胰岛和造血谱系中的作用正在探索中。此外,MEN1的组织特异性转基因表达和敲除模型正在果蝇中开发。这些模型应该有助于理解menin的功能作用,并提出可能的治疗方向。
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 }}
settara chandrasekharappa其他文献
settara chandrasekharappa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('settara chandrasekharappa', 18)}}的其他基金
相似海外基金
Manipulation of stem cell differentiation by noninvasive electrical stimulus
通过无创电刺激操纵干细胞分化
- 批准号:
7230114 - 财政年份:2006
- 资助金额:
-- - 项目类别:
Recombinant Ab markers for stem cell differentiation
用于干细胞分化的重组抗体标记
- 批准号:
7051793 - 财政年份:2006
- 资助金额:
-- - 项目类别:
Regulation of cell differentiation and stimulation on D-aglucse displayed dendrimer surface
D-alucse 展示的树枝状聚合物表面上细胞分化和刺激的调节
- 批准号:
17360398 - 财政年份:2005
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (B)
DNA ARRAY ANALYSIS OF STEM CELL DIFFERENTIATION II
干细胞分化的 DNA 阵列分析 II
- 批准号:
6972808 - 财政年份:2004
- 资助金额:
-- - 项目类别:
Development of fundamental basis for embryo-biotechnology in next generation by clarifying the regulatory mechanisms of cell differentiation and apoptosis of oocytes
阐明卵母细胞分化和凋亡的调控机制,为下一代胚胎生物技术奠定基础
- 批准号:
16108003 - 财政年份:2004
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (S)
Small Molecular Regulation of Beta-Cell Differentiation
β 细胞分化的小分子调控
- 批准号:
6827525 - 财政年份:2004
- 资助金额:
-- - 项目类别:
Engineer/Embryonic Stem Cell Differentiation/Hepatocytes
工程师/胚胎干细胞分化/肝细胞
- 批准号:
6846547 - 财政年份:2004
- 资助金额:
-- - 项目类别: