Establishing a Role for Kinesin-8 in Mammalian Germ Line Development

确定 Kinesin-8 在哺乳动物种系发育中的作用

基本信息

批准号：
8769699
负责人：
LAURA G REINHOLDT
金额：
$ 8.75万
依托单位：
JACKSON LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-17 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8769699
关键词：
Ablation Alleles Animals Anovulation Apoptosis Assisted Reproductive Technology Biological Buffers Cell Cycle Arrest Cell Proliferation Cell division Chromosomes Collaborations Colorectal Cancer Couples Data Data Set Defect Development Embryo Female infertility Fertility Fetal Development Fibroblasts Foundations Gametogenesis Genes Genetic Genetic Screening Genome Genomics Germ Cells Germ Lines Goals Gonadal structure High-Throughput Nucleotide Sequencing Inbred Strains Mice Individual Induced Mutation Infertility Kinesin Lead Life Maintenance Male Infertility Maps Metaphase Plate Microtubules Molecular Motor Mus Mutant Strains Mice Mutation Oligospermia Organism Pathway interactions Penetrance Phenotype Process Proteins Publishing Quantitative Trait Loci Regulatory Element Research Research Project Grants Role Secondary to Somatic Cell Stem cells Testing Time United States Universities Vermont Woman cell type economic impact fetal malignant breast neoplasm men mutant neuronal cell body overexpression programs public health relevance research study restoration tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): This small research project focuses on the role of kinesin 8, Kif18A, which has an essential function in cell division and is broadly expressed, yet is uniquely required in the developing germ line. Mutations in mammalian Kif18A lead to germ cell depletion and ultimately infertility; however, infertility in mutant mice is not fully penetrat and is dependent on strain background. Therefore, there are genetic factors that ameliorate infertility in the context of Kif18A ablation. The unique role of Kif18a in germ line development has only recently been revealed and a mechanism for Kif18a function in the germ line has not been established. The overall goal of this small research project is to provide the basic biological data required to establish the mechanism by which Kif18A functions in germ line development and to create a genetic dataset for the discovery of the molecular pathways that modulate Kif18A dependent germ cell depletion. These data will contribute to the foundation of a larger research program focused on the specialization of germ cell division in the mammalian germ line, where maintenance of genome integrity is integral to gametogenesis and, critically, fertility.

描述（由申请人提供）：这个小型研究项目的重点是驱动蛋白8，KIF18A的作用，KIF18A在细胞分裂中具有重要功能，并且广泛表达，但在发育中的生殖系中是独特的。哺乳动物KIF18A的突变导致生殖细胞耗竭并最终不育症。但是，突变小鼠的不育症不是完全渗透的，并且取决于应变背景。因此，在KIF18A消融的背景下，有一些遗传因素可以改善不育。 KIF18A在生殖系发育中的独特作用直到最近才揭示，并且尚未确定生殖系中KIF18A功能的机制。这个小型研究项目的总体目标是提供基本的生物学数据，以建立KIF18A在生殖线发育中起作用并创建一个遗传数据集的机制，以发现调节KIF18A依赖生殖细胞耗竭的分子途径。这些数据将有助于较大的研究计划的基础，该研究计划着重于哺乳动物生殖系中生殖细胞分裂的专业化，其中基因组完整性的维持是配子发生的必不可少的，并且至关重要的是生育能力。