DEVELOPMENTAL RATES ARE DEFINED BY CHROMOSOMAL REGIONS

发育速度由染色体区域决定

• 批准号: 2862109
• 负责人: SIMON KLEBANOV
• 金额: $ 3.84万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2862109
• 关键词: aging; animal puberty; developmental genetics; genetic polymorphism; genetic strain; laboratory mouse; polymerase chain reaction; quantitative trait loci

Gestation interval, age at maturity and life span vary proportionally across mammalian species. This intriguing observation is the basis for the hypothesis that a set of master clocks exists, which determines rates of transition through different life cycle stages. Interspecies comparisons, however, do not allow a direct genetic analysis of determinants of timing because mammalian species generally do not interbreed. We have recently characterized a number of mouse strains whose ages of the onset of reproduction are drastically different. Two interstrain crosses between the slowest and fastest developing strains will be produced and for each individual timing of sexual maturation and several other developmental milestones will be evaluated. We will then test the hypothesis that a single or a few QTL(s) exist(s) with a large effect on timing of the onset of reproduction. In the second part of the proposal we will produce another two crosses between strains which have been shown to have different alleles increasing maximal life span. In these two crosses we will also look for QTLs affecting developmental timing and will test the hypothesis that some QTLs that affect timing of sexual maturation superimpose with QTLs affecting aging, suggesting the existence of genes with pleiotropic effects on development and aging.

不同哺乳动物物种的妊娠间隔、成熟年龄和寿命成比例地变化。 这一有趣的观察结果是存在一组主时钟的假设的基础，它决定了不同生命周期阶段的过渡速率。 然而，种间比较不允许对时间决定因素进行直接遗传分析，因为哺乳动物物种通常不会杂交。 我们最近对一些小鼠品系进行了表征，它们的繁殖开始年龄截然不同。 将在最慢和最快发育品系之间产生两个品系间杂交，并且将评估每个个体的性成熟时间和其他几个发育里程碑。 然后，我们将检验以下假设：存在一个或几个 QTL，对繁殖开始时间有很大影响。 在提案的第二部分中，我们将在菌株之间产生另外两个杂交，这些菌株已被证明具有不同的等位基因，可增加最大寿命。 在这两个杂交中，我们还将寻找影响发育时间的QTL，并检验以下假设：一些影响性成熟时间的QTL与影响衰老的QTL叠加，表明存在对发育和衰老具有多效性影响的基因。