Heart development following genetic inactivation of Lmp4

Lmp4 基因失活后的心脏发育

基本信息

项目摘要

DESCRIPTION (provided by applicant): The proposed studies determine the biological function of Lmp4 in heart development, alone and in association with Tbx5. This may provide new explanations for the wide range of phenotypes observed in Holt-Oram syndrome patients. To address the functional role of Lmp4 in heart development, we genetically inactivated the gene in the mouse. Utilizing the Lmp4 knockout mouse model, the proposed research will specifically test the hypothesis that Lmp4 functions as a regulator of Tbx5 subcellular localization in heart and coronary vasculature development. Lmp4 and Tbx5 expression will be analyzed in Lmp4 mutant mice, in comparison to wild type mice, providing insight into whether Lmp4 has a direct influence on Tbx5 subcellular distribution in an Lmp4 dosage dependent manner. The morphological phenotypes associated with genetic Lmp4 inactivation in the developing mouse heart will be analyzed in conjunction with Lmp4 and Tbx5 expression domains. This will determine whether the phenotypes are a direct result of compromised Lmp4 expression, or an indirect effect via altered Tbx5 subcellular localization. Primary epicardial cells cultured from homozygous Lmp4 mouse hearts will be used to determine the mechanistic function of Lmp4 alone and in association with Tbx5. The migratory behavior of the Lmp4 mutant cells will be assessed following rescue by transfection with full-length Lmp4 and rescue by transfection with Lmp4 constructs that lack the LIM3 domain Tbx5 binds. Lmp4 is a member of the PDZ-LIM family of proteins that function in critical biological processes such as organ development. Tbx5 is a member of the T-box family of transcription factors that has critical roles in many aspects of organogenesis. The overall goal of this proposed research is to elucidate the functional role of the interaction of Lmp4 and Tbx5 in heart development, which may provide new insights into heart/limb phenotypes observed in Holt-Oram syndrome.
描述(由申请人提供):拟议的研究确定了Lmp4在心脏发育中的生物学功能,单独和与Tbx5相关。这可能为Holt-Oram综合征患者观察到的广泛表型提供新的解释。为了解决Lmp4在心脏发育中的功能作用,我们在小鼠中对该基因进行了基因失活。利用Lmp4基因敲除的小鼠模型,这项拟议的研究将专门测试Lmp4作为Tbx5亚细胞定位调节器在心脏和冠状动脉血管发育中的作用的假设。将分析Lmp4突变小鼠和Tbx5的表达,并与野生型小鼠进行比较,从而深入了解Lmp4是否以Lmp4剂量依赖的方式直接影响Tbx5亚细胞分布。与发育中的小鼠心脏中Lmp4基因失活相关的形态表型将结合Lmp4和Tbx5的表达结构域进行分析。这将决定表型是Lmp4表达受损的直接结果,还是通过改变Tbx5亚细胞定位的间接影响。从纯合的Lmp4小鼠心脏培养的原代心外膜细胞将被用来单独确定Lmp4的机械功能以及与Tbx5联合使用。Lmp4突变细胞的迁移行为将通过全长Lmp4的转染法和缺乏LIM3结构域Tbx5结合的Lmp4构建物的转染法进行评估。LMP4是PDZ-LIM蛋白家族的成员,在器官发育等关键生物学过程中发挥作用。Tbx5是T-box转录因子家族中的一员,在器官发生的许多方面起着关键作用。这项拟议研究的总体目标是阐明Lmp4和Tbx5相互作用在心脏发育中的功能作用,这可能为在Holt-Oram综合征中观察到的心脏/肢体表型提供新的见解。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Pdlim7 Regulates Arf6-Dependent Actin Dynamics and Is Required for Platelet-Mediated Thrombosis in Mice.
  • DOI:
    10.1371/journal.pone.0164042
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Urban AE;Quick EO;Miller KP;Krcmery J;Simon HG
  • 通讯作者:
    Simon HG
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Jennifer K Krcmery其他文献

Jennifer K Krcmery的其他文献

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{{ truncateString('Jennifer K Krcmery', 18)}}的其他基金

Heart development following genetic inactivation of Lmp4
Lmp4 基因失活后的心脏发育
  • 批准号:
    7671485
  • 财政年份:
    2007
  • 资助金额:
    $ 2.86万
  • 项目类别:
Heart development following genetic inactivation of Lmp4
Lmp4 基因失活后的心脏发育
  • 批准号:
    7907837
  • 财政年份:
    2007
  • 资助金额:
    $ 2.86万
  • 项目类别:
Heart development following genetic inactivation of Lmp4
Lmp4 基因失活后的心脏发育
  • 批准号:
    7496622
  • 财政年份:
    2007
  • 资助金额:
    $ 2.86万
  • 项目类别:
Heart development following genetic inactivation of Lmp4
Lmp4 基因失活后的心脏发育
  • 批准号:
    7321879
  • 财政年份:
    2007
  • 资助金额:
    $ 2.86万
  • 项目类别:

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