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Identify genetic mechanisms that regulate female sexual maturation

确定调节女性性成熟的遗传机制

基本信息

批准号：
8842914
负责人：
Rong Yuan
金额：
$ 7.15万
依托单位：
SOUTHERN ILLINOIS UNIVERSITY SCH OF MED
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：
2014-05-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8842914
关键词：
Age Age at Menarche Aging Aging-Related Process Bioinformatics Biological Biometry Candidate Disease Gene Chromosome Mapping Code Complex Coronary heart disease DNA DNA Resequencing Data Diabetes Mellitus Disease Ensure Family Female Foundations Future Genes Genetic Genetic Variation Genotype Haplotypes Health House mice Human Human Genome Inbred Strain Inbred Strains Mice Insulin-Like Growth Factor I Investigation Life Longevity Malignant Female Reproductive System Neoplasm Malignant neoplasm of ovary Measures Methods Mouse Strains Mus Obesity Organism Osteoporosis Outcome Pathologic Processes Plasma Proprotein Convertases Quantitative Trait Loci Regulation Reproduction Risk Sampling Sexual Maturation Solid Stroke Subtilisins Surveys Time Tissue Inhibitor of Metalloproteinase-3 Vagina Variant Woman age related base density differential expression genome sequencing genome wide association study human NRIP1 protein kexin life history malignant breast neoplasm mortality new therapeutic target novel progenitor programs success trait translational medicine

项目摘要

DESCRIPTION (provided by applicant): Sexual maturation is key to the evolutionary success of an organism. Evolutionary hypotheses predict that slower but fully functional female reproduction indicates slower aging and associates with extended lifespan. In humans, the age at menarche (AAM) is associated with significant health conditions later in life, and at least half the variation in AAM is determined by genetic factors that are not yet fully understood. Recently, we systematically measured age of female sexual maturation (FSM) in 32 mouse strains. The age of FSM varied dramatically among these strains, and delayed FSM correlated with lower circulating insulin like growth factor 1 (IGF1) and extended longevity. Some strains, however, had delayed FSM but higher IGF1, showing that circulating IGF1 dependent and independent mechanisms are involved. To identify the underlying genetic mechanisms, we generated 7 mouse crosses from 15 inbred strains that broadly represent the genetic diversity and variation in age of FSM across the mouse family. We have collected the age of FSM, plasma and DNA samples for 1,962 females of these crosses. And using genetic and bioinformatic methods, we identified a promising candidate gene, proprotein convertase subtilisin/kexin type 2 (Pcsk2). In this project, we propose to identify novel regulatory candidates of female sexual maturation. This project will lay a solid foundation for future investigation of FSM and its related diseases, s well as the aging process itself.

描述（由申请人提供）：性成熟是生物体进化成功的关键。进化假说预测，女性生殖速度较慢但功能齐全，表明衰老速度较慢，并且与寿命延长有关。在人类中，初潮年龄 (AAM) 与晚年的重大健康状况相关，并且至少一半 AAM 的变异是由尚未完全了解的遗传因素决定的。最近，我们系统地测量了 32 种小鼠品系的雌性性成熟 (FSM) 年龄。这些菌株的 FSM 年龄差异很大，并且 FSM 延迟与循环胰岛素样生长因子 1 (IGF1) 降低和寿命延长相关。然而，一些菌株的 FSM 延迟，但 IGF1 较高，表明涉及循环 IGF1 依赖和独立机制。为了确定潜在的遗传机制，我们从 15 个近交系中产生了 7 个小鼠杂交，这些小鼠广泛代表了整个小鼠家族的遗传多样性和 FSM 年龄的变化。我们收集了 1,962 名杂交雌性的 FSM 年龄、血浆和 DNA 样本。利用遗传和生物信息学方法，我们确定了一个有前途的候选基因，前蛋白转化酶枯草杆菌蛋白酶/kexin 2 型 (Pcsk2)。在这个项目中，我们建议确定女性性成熟的新监管候选者。该项目将为未来研究 FSM 及其相关疾病以及衰老过程本身奠定坚实的基础。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Deletion of Nrip1 Extends Female Mice Longevity, Increases Autophagy, and Delays Cell Senescence.

Nrip1 的缺失可延长雌性小鼠的寿命、增强自噬并延缓细胞衰老。

DOI：
10.1093/gerona/glx257
发表时间：
2018
期刊：
The journals of gerontology. Series A, Biological sciences and medical sciences
影响因子：
0
作者：
Wang,Jinyu;Chen,Xundi;Osland,Jared;Gerber,SkylerJ;Luan,Chao;Delfino,Kristin;Goodwin,Leslie;Yuan,Rong
通讯作者：
Yuan,Rong

Potentiation of Psoriasis-Like Inflammation by PCSK9.