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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）：性成熟是生物进化成功的关键。进化假说预测，较慢但功能齐全的女性生殖表明衰老较慢，并与延长寿命有关。在人类中，初潮年龄（AAM）与以后生活中的重大健康状况有关，至少有一半的人认为， 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个品系小鼠的雌性性成熟年龄（FSM）。FSM的年龄在这些菌株中变化很大，并且延迟FSM与较低的循环胰岛素样生长因子1（IGF 1）和延长寿命相关。然而，一些菌株具有延迟的FSM，但具有较高的IGF 1，表明涉及循环IGF 1依赖性和非依赖性机制。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，这些近交系广泛代表了小鼠家族中FSM的遗传多样性和年龄变化。我们收集了1,962名这些杂交后代的FSM年龄、血浆和DNA样本。利用遗传学和生物信息学方法，我们鉴定了一个有希望的候选基因，前蛋白转化酶枯草杆菌蛋白酶/kexin 2（Pcsk 2）。在这个项目中，我们建议确定新的女性性成熟的调节候选人。本研究为进一步研究FSM及其相关疾病以及衰老过程奠定了基础。

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.