A unique mouse strain expressing Cre recombinase for tissue-specific analysis of gene function in palate and kidney development

A unique mouse strain expressing Cre recombinase for tissue-specific analysis of gene function in palate and kidney development
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DOI:
10.1002/dvg.20334
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发表时间:
2007-10-01
期刊:
影响因子:
1.5
通讯作者:
Jiang, Rulang
Jiang, Rulang
中科院分区:
生物学4区
文献类型:
--
作者:
Lan, Yu;Wang, Oingru;Jiang, Rulang

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哺乳动物腭的发育是一个多步骤的过程,包括最初的两侧向下生长的腭架从口腔侧的上颌突,随后阶段特定的腭架海拔到水平位置以上的发展中的舌头和随后的双边腭架在中线融合,形成完整的口腔的屋顶。虽然许多基因的突变与腭裂的发病机制有关,但调节腭架生长、形成模式和升高的分子机制还不清楚。在突变小鼠模型中控制腭发育的分子机制的遗传学研究通常由于早期胚胎致死或严重颅面畸形而变得复杂。我们在这里报告的发展,小鼠品系的组织特异性分析基因功能的腭发展。我们通过基因打靶将IresCre双顺反子表达盒插入小鼠Osr 2基因的31个非翻译区。我们表明,在交叉的R26 R报告小鼠,Cre表达的Osr 2(Irescre)敲入等位基因激活P-半乳糖苷酶的表达,特别是在整个发展中的腭间充质从腭架生长的发病。此外,Osr 2(Irescre)小鼠显示排他性。Cre介导的重组在肾小球组织中来自后肾间充质,在发育中的后肾的其他上皮和间充质组织中完全没有Cre活性。这些数据表明,Osr 2(Irescre)敲入小鼠提供了一个独特的工具,组织特异性研究的分子机制调节腭和肾脏的发展。
Mammalian palate development is a multistep process, involving initial bilateral downward outgrowth of the palatal shelves from the oral side of the maxillary processes, followed by stage-specific palatal shelf elevation to the horizontal position above the developing tongue and subsequent fusion of the bilateral palatal shelves at the midline to form the intact roof of the oral cavity. While mutations in many genes have been associated with cleft palate pathogenesis, the mo lecular mechanisms regulating palatal shelf growth, patterning, and elevation are not well understood. Genetic studies of the molecular mechanisms controlling palate development in mutant mouse models are often complicated by early embryonic lethality or gross craniofacial malformation. We report here the development of a mouse strain for tissue-specific analysis of gene function in palate development. We inserted an IresCre bicistronic expression cassette into the 31 untranslated region of the mouse Osr2 gene through gene targeting. We show, upon crossing to the R26R reporter mice, that Cre expression from the Osr2(Irescre) knockin allele activated P-galactosidase expression specifically throughout the developing palatal mesenchyme from the onset of palatal shelf outgrowth. In addition, the Osr2(Irescre) mice display exclusive. Cre-mediated recombination in the glomeruli tissues derived from the metanephric mesenchyme and complete absence of Cre activity in other epithelial and mesenchymal tissues in the developing metanephric kidney. These data indicate that the Osr2(Irescre) knockin mice provide a unique tool for tissue specific studies of the molecular mechanisms regulating palate and kidney development.