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Genetic Analysis of the Hippo Signaling Pathway in the Mouse Mammary Gland

小鼠乳腺 Hippo 信号通路的遗传分析

基本信息

批准号：
7894938
负责人：
Randy L. Johnson
金额：
$ 38.04万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7894938
关键词：
Adaptor Signaling Protein Address Alleles Animals Apoptosis Attenuated Biological Assay Biological Process Cell Count Cell Cycle Cell Proliferation Cells Data Development Differentiation and Growth Disease Doxycycline Drosophila genus Embryo Epithelial Equilibrium Exhibits Female Gene Targeting Genetic Growth Growth and Development function Health Hormones Human Incidence Lead Malignant Neoplasms Mammalian Genetics Mammals Mammary Tumorigenesis Mammary gland Mediating Methods Modeling Molecular Multipotent Stem Cells Mus Mutant Strains Mice Organ Organ Size Organism Orthologous Gene Pathway interactions Phenotype Play Population Pregnancy Process Protein-Serine-Threonine Kinases Reagent Regulation Research Research Project Grants Role Series Signal Pathway Signal Transduction Staging Stem cells Stimulus Testing Tissues Transgenes base cancer cell cell growth gain of function gene conservation genetic analysis imaginal disc insight mammary epithelium man mouse model mutant novel null mutation prevent progenitor stem tumor tumor initiation tumorigenesis

项目摘要

How animals regulate organ size is unknown. Recent studies in Drosophila point towards a novel signaling pathway called “hippo” as an important regulator of organ growth. Cells that are mutant for components of the hippo signaling pathway exhibit features of overgrowth accompanied by increased proliferation and attenuated apoptosis. In mammals, conserved orthologs of each hippo pathway component have been found. However, the role of hippo signaling in mammals has not been explored. Here we propose to define the role of hippo signaling in the mouse mammary gland. The mouse mammary gland is uniquely suited for these studies as it undergoes hormone-induced waves of proliferation and apoptosis during normal development and pregnancy. Moreover, the mammary gland is dispensable for viability, allowing application of conditional approaches for assessment of hippo function. We have generated conditional alleles at several key core hippo pathway components and are in the process of analyzing the phenotype of animals that have reduced or absent hippo signaling in the mammary gland. Preliminary data suggests that as in Drosophila, hippo signaling plays an important role in preventing overgrowth. We will extend these preliminary observations by systematically deleting core components of the hippo signaling pathway in the mouse mammary gland and by applying a series of cytological, cell-based, and molecular methods to define both the requirement for hippo signaling and to define how hippo signaling controls mammary gland growth on a molecular level. In summary, the proposed research will define functions for hippo signaling in the normal mammary gland and thus provide novel insight into mechanism of organ size control in mammalian tissues.

动物如何调节器官大小尚不清楚。最近对果蝇的研究表明