Characterization of a novel fibroblast growth factor 10 (Fgf10) knock-in mouse line to target mesenchymal progenitors during embryonic development.
Characterization of a novel fibroblast growth factor 10 (Fgf10) knock-in mouse line to target mesenchymal progenitors during embryonic development.
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在胚胎发育过程中，新型成纤维细胞生长因子10（FGF10）敲入小鼠系的表征。
DOI：
10.1371/journal.pone.0038452
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bellusci S
中科院分区：
文献类型：
--
作者：
El Agha E;Al Alam D;Carraro G;MacKenzie B;Goth K;De Langhe SP;Voswinckel R;Hajihosseini MK;Rehan VK;Bellusci S
成纤维细胞生长因子10(Fgf10)是小鼠发育过程中各种器官发生程序的关键调节因子，尤其是分枝形态发生。FGF10基因缺失的小鼠患有肺和肢体发育不全以及盲肠和结肠闭锁，因此无法存活。到目前为止，Mlcv1v-nLacZ-24转基因小鼠品系(简称Fgf10LacZ)是唯一能够对Fgf10阳性细胞进行瞬时谱系追踪的品系，它在Fgf10基因外显子1上游插入了114kb的LacZ片段。在这里，我们描述了一个新的Fgf10Cre-ERT2敲入系(Fgf10iCre)，它是在Fgf10基因外显子1的ATG框架内引入了Cre-ERT2-IRES-YFP盒。我们的研究表明，Cre-ERT2插入扰乱了Fgf10的功能。然而，给Fgf10iCre；Tomatoflox双转基因胚胎或成年小鼠注射他莫昔芬会导致Fgf10阳性细胞的特异性标记，这可以在时间和空间上进行谱系追踪。此外，我们还证明了Fgf10iCre系可以在早期发育阶段以可诱导的方式用于条件性基因失活。我们还提供了证据表明，位于Fgf10基因第一内含子的转录因子对于长期维持Fgf10的表达至关重要。因此，Fgf10iCre品系应该作为一个强大的工具，以受控和阶段特异性的方式探索Fgf10的功能。
Fibroblast growth factor 10 (Fgf10) is a key regulator of diverse organogenetic programs during mouse development, particularly branching morphogenesis. Fgf10-null mice suffer from lung and limb agenesis as well as cecal and colonic atresia and are thus not viable. To date, the Mlcv1v-nLacZ-24 transgenic mouse strain (referred to as Fgf10LacZ), which carries a LacZ insertion 114 kb upstream of exon 1 of Fgf10 gene, has been the only strain to allow transient lineage tracing of Fgf10-positive cells. Here, we describe a novel Fgf10Cre-ERT2 knock-in line (Fgf10iCre) in which a Cre-ERT2-IRES-YFP cassette has been introduced in frame with the ATG of exon 1 of Fgf10 gene. Our studies show that Cre-ERT2 insertion disrupts Fgf10 function. However, administration of tamoxifen to Fgf10iCre; Tomatoflox double transgenic embryos or adult mice results in specific labeling of Fgf10-positive cells, which can be lineage-traced temporally and spatially. Moreover, we show that the Fgf10iCre line can be used for conditional gene inactivation in an inducible fashion during early developmental stages. We also provide evidence that transcription factors located in the first intron of Fgf10 gene are critical for maintaining Fgf10 expression over time. Thus, the Fgf10iCre line should serve as a powerful tool to explore the functions of Fgf10 in a controlled and stage-specific manner.
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影响因子：
4.6
作者：
Alvarez, Y;Alonso, MT;Schimmang, T
通讯作者：
Schimmang, T
影响因子：
4.6
作者：
Mailleux, AA;Kelly, R;Bellusci, S
通讯作者：
Bellusci, S
影响因子：
64.8
作者：
Santos-Rosa, H;Schneider, R;Kouzarides, T
通讯作者：
Kouzarides, T
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
影响因子：
3.7
作者：
Al Alam D;Green M;Tabatabai Irani R;Parsa S;Danopoulos S;Sala FG;Branch J;El Agha E;Tiozzo C;Voswinckel R;Jesudason EC;Warburton D;Bellusci S
通讯作者：
Bellusci S