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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Genetic coregulation of age of female sexual maturation and lifespan through circulating IGF1 among inbred mouse strains
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Genetic coregulation of age of female sexual maturation and lifespan through circulating IGF1 among inbred mouse strains

机译：自交小鼠品系中循环IGF1对女性性成熟年龄和寿命的遗传调控

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摘要

We previously reported that mouse strains with lower circulating insulin-like growth factor 1 (IGF1) level at 6 mo have significantly extended longevity. Here we report that strains with lower IGF1 have significantly delayed age of female sexual maturation, measured by vaginal patency (VP). Among strains with normal lifespans (mean lifespan >600 d), delayed age of VP associated with greater longevity (P = 0.015), suggesting a genetically regulated tradeoff at least partly mediated by IGF1. Supporting this hypothesis, C57BL/6J females had 9% lower IGF1, 6% delayed age of VP, and 24% extended lifespan compared with C57BL/6J.C3H/HeJ-lgf1, which carries a C3H/HeJ allele on chromosome (Chr) 10 that increases IGF1. To identify genetic loci/genes that regulate female sexual maturation, including loci that mediate lifespan tradeoffs, we performed haplotype association mapping for age of VP and identified significant loci on Chrs 4 (Vpq1) and 16 (Vpq2 and 3). At each locus, wild-derived strains share a unique haplotype that associates with delayed VP. Substitution of Chr 16 of C57BL/6J with Chr 16 from a wild-derived strain significantly reduced IGF1 and delayed VP. Strains with a wild-derived allele at Vpq3 have significantly extended longevity compared with strains with other alleles. Bioin-formatic analysis identified Nripi at Vpq3 as a candidate gene. Nrip1~(-/-) females have significantly reduced IGF1 and delayed age of VP compared with Nrip1~(+/+)females. We conclude that IGF1 may coregulate female sexual maturation and longevity; wild-derived strains carry specific alleles that delay sexual maturation; and Nripi is involved in regulating sexual maturation and may affect longevity by regulating IGF1 level.
机译：我们先前曾报道，在6个月时具有较低的循环胰岛素样生长因子1（IGF1）水平的小鼠品系具有显着延长的寿命。在这里我们报告说，具有较低IGF1的菌株通过阴道通畅（VP）可以显着延迟女性性成熟的年龄。在具有正常寿命（平均寿命> 600 d）的菌株中，VP的延迟年龄与更长的寿命相关（P = 0.015），这表明遗传调控的权衡至少部分地由IGF1介导。支持这一假设的C57BL / 6J雌性与C57BL / 6J.C3H / HeJ-lgf1相比，在染色体（Chr）上携带C3H / HeJ等位基因，女性IGF1低9％，VP延迟年龄6％，寿命延长24％。 10增加IGF1。为了确定调节女性性成熟的遗传基因座/基因，包括介导寿命折衷的基因座，我们对VP的年龄进行了单倍型关联作图，并确定了Chrs 4（Vpq1）和16（Vpq2和3）上的重要基因座。在每个基因座上，野生菌株均具有独特的单倍型，与延迟VP相关。用野生来源菌株的Chr 16替代C57BL / 6J的Chr 16，可显着降低IGF1并延迟VP。与具有其他等位基因的菌株相比，在Vpq3处具有野生来源的等位基因的菌株的寿命大大延长。生物信息学分析确定Vpq3处的Nripi为候选基因。与Nrip1〜（+ / +）雌性相比，Nrip1〜（-/-）雌性具有显着降低的IGF1和VP年龄。我们得出的结论是，IGF1可以整合女性的性成熟和长寿。野生菌株携带特定的等位基因，可延迟性成熟。 Nripi参与调节性成熟，并可能通过调节IGF1水平而影响寿命。

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  • 作者

    Rong Yuan; Qingying Mencf; Jaya Nautiyal; Kevin Flurkey; Shirng-Wern Tsaih; Rebecca Krier; Malcolm G. Parker; David E. Harrison; Beverly Paigen;

  • 作者单位

    The Jackson Laboratory, Bar Harbor, ME 04609;

    The Jackson Laboratory, Bar Harbor, ME 04609;

    Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, London W12 ONN, United Kingdom;

    The Jackson Laboratory, Bar Harbor, ME 04609;

    Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wl 53226;

    The Jackson Laboratory, Bar Harbor, ME 04609, Department of Infectious Disease and Immunology, Loyola University Chicago Stritch School of Medicine, Chicago, IL 60153;

    Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, London W12 ONN, United Kingdom;

    The Jackson Laboratory, Bar Harbor, ME 04609;

    The Jackson Laboratory, Bar Harbor, ME 04609;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    aging; reproduction; hormone;

    机译：老化;再生产;激素;

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