System for tamoxifen-inducible expression of Cre-recombinase from the Foxa2 locus in mice

System for tamoxifen-inducible expression of Cre-recombinase from the Foxa2 locus in mice
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DOI:
10.1002/dvdy.21415
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发表时间:
2008-02-01
影响因子:
2.5
通讯作者:
Moon, Anne M.
Moon, Anne M.
中科院分区:
生物学3区
文献类型:
--
作者:
Park, Eon Joo;Sun, Xiaoxia;Moon, Anne M.

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为了研究内胚层、脊索和底板中关键转录因子网络、生长因子和信号分子的作用,我们开发了一种可诱导的Cre表达系统,用于改变该组织中的基因功能。我们产生了一个等位基因的Foxa2指导他莫昔芬调节的Cre的Foxa2表达域(Foxa2(mcm))。Foxa2(mcm)的活性再现了内胚层、脊索和底板中的内源性Foxa2表达。系统在给定组织类型中的效率是剂量和时间依赖性的。通过比较通过口服管饲法与腹膜内注射施用他莫昔芬后Cre活性的效率和位置,我们发现口服管饲法实现更快速、稳健的重组,具有更小的胚胎毒性。该系统将用于在小鼠胚胎发生和胎儿发育的多个阶段控制floxed等位基因的活性。
To study the roles of key transcription factor networks, growth factors, and signaling molecules in the endoderm, notochord, and floorplate, we developed an inducible Cre-expressing system for altering gene function in this tissue. We generated an allele of Foxa2 that directs a tamoxifen-regulated Cre in the Foxa2 expression domain (Foxa2(mcm)). Activity of Foxa2(mcm) recapitulates endogenous Foxa2 expression in endoderm, notochord, and floorplate. Efficiency of the system in a given tissue type was dose- and timing-dependent. By comparing efficiency and location of Cre activity after administration of tamoxifen by oral gavage vs. intraperitoneal injection, we found that oral gavage achieves more rapid, robust recombination with less embryonic toxicity. This system will be useful for controlling the activity of floxed alleles at multiple stages of mouse embryogenesis and fetal development.