Co-localizing Quantitative Trait Loci for Bone Mineral Density and HDL in Mice

小鼠骨矿物质密度和 HDL 的定量性状基因座的共定位

• 批准号: 8894967
• 负责人: Cheryl Lynne Ackert-Bicknell
• 金额: $ 25.99万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8894967
• 关键词: Co; localizing; Quantitative; Trait; Loci

Project Summary/Abstract: Half of all Americans either have or are at serious risk for developing osteoporosis. Bone mineral density (BMD) can be readily measured in a clinical setting, and low BMD is associated with increased risk of osteoporotic fracture. Cardiovascular disease (CVD) a major cause of death in industrialized societies, and it is well established that raising HDL cholesterol reduces the risk of cardiovascular disease. Studies have shown that low BMD can be used as an independent predictor of CVD, and patients with CVD are more likely to have low BMD. Smoking, lack of exercise and eating a high fat “Western” diet increases the risk of developing both CVD and osteoporosis. Together these suggest that there may be shared causes for these two diseases. Both BMD and serum HDL levels have been shown to be genetically regulated. Preliminary studies in humans have suggested the existence of shared genetic causes for both of these phenotypes, but, as environmental and lifestyle factors influence both BMD and serum HDL levels, identifying the genetic link between CVD and osteoporosis has been difficult. The mouse is an excellent model for mapping genes that underlie complex traits, and unlike in human studies, environment can be controlled and modulated as needed in studies using the mouse. Two quantitative trait loci (QTL) for BMD have been identified on mouse Chromosome 1 and 8 that are coincident for QTL for serum HDL. Furthermore, both of these BMD QTL interact with dietary cholesterol intake. The Chr 1 QTL has been narrowed down to two genes and the Chr 8 QTL has been narrowed down to 4 candidate genes. In this application, transgenic mice for the candidate genes on Chr 1 will be used to confirm that: 1) that these genes impact BMD; 2) this QTL interacts with dietary cholesterol intake to affect BMD; and 3) this same genes do or do not regulates serum HDL levels. In the second Aim, the gene underlying the BMD QTL on Chr 8 will be identified and the hypothesis that a single gene at this locus regulates both the BMD and HDL QTL will be confirmed.

项目总结/文摘:

项目成果

Passenger Gene Mutations: Unwanted Guests in Genetically Modified Mice.

• DOI: 10.1002/jbmr.2772
• 发表时间: 2016-02
• 期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
• 作者: Ackert-Bicknell CL;Rosen CJ
• 通讯作者: Rosen CJ

Genetics of aging bone.

• DOI: 10.1007/s00335-016-9650-y
• 发表时间: 2016-08
• 期刊: Mammalian genome : official journal of the International Mammalian Genome Society
• 作者: Adams DJ;Rowe DW;Ackert-Bicknell CL
• 通讯作者: Ackert-Bicknell CL

HDL cholesterol and bone mineral density: is there a genetic link?

• DOI: 10.1016/j.bone.2011.07.002
• 发表时间: 2012-02
• 期刊: BONE
• 影响因子: 4.1
• 作者: Ackert-Bicknell, Cheryl L.

Mapping of Craniofacial Traits in Outbred Mice Identifies Major Developmental Genes Involved in Shape Determination.

远交小鼠颅面特征图谱鉴定了参与形状决定的主要发育基因。

• DOI: 10.1371/journal.pgen.1005607
• 发表时间: 2015
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Pallares,LuisaF;Carbonetto,Peter;Gopalakrishnan,Shyam;Parker,ClarissaC;Ackert-Bicknell,CherylL;Palmer,AbrahamA;Tautz,Diethard
• 通讯作者: Tautz,Diethard

Impact of the environment on the skeleton: is it modulated by genetic factors?

• DOI: 10.1007/s11914-013-0151-6
• 发表时间: 2013-09
• 期刊: CURRENT OSTEOPOROSIS REPORTS
• 影响因子: 4.3
• 作者: Ackert-Bicknell, Cheryl L.;Karasik, David
• 通讯作者: Karasik, David