Conditional deletions refine the embryonic requirement for Dlk1.
Conditional deletions refine the embryonic requirement for Dlk1.
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DOI：
10.1016/j.mod.2012.09.010
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发表时间：
2013-02
影响因子：
2.6
通讯作者：
Schmidt, Jennifer V.
中科院分区：
文献类型：
--
作者：
Appelbe, Oliver K.;Yevtodiyenko, Aleksey;Muniz-Talavera, Hilmarie;Schmidt, Jennifer V.
大量研究表明，Delta-like 1（DLK 1）是一种跨膜蛋白，与Notch配体具有同源性，参与胚胎的生长和分化。Dlk 1的表达是广泛的，虽然不是普遍存在的，在早期发展，但仅限于一些特定的细胞类型在成人。成人Dlk 1表达组织包括胰腺的胰岛素产生β细胞和脑垂体的生长激素产生生长激素细胞。先前产生的Dlk 1无效小鼠（Dlk 1 Sul-pat），显示部分渗透新生儿致死率和复杂的模式的发展和成人表型。在这里，我们描述了一个有条件的Dlk 1小鼠系（Dlk 1flox），以促进细胞类型特异性删除的Dlk 1基因，提供了一个强大的系统来探索Dlk 1空表型的各个方面。使用四种组织特异性Cre小鼠品系在胰腺β细胞、垂体生长激素细胞以及胚胎和胎盘的内皮细胞（Dlk 1表型的关键候选者）中产生单独的Dlk 1缺失。与预期相反，所有这些条件小鼠都是完全存活的，并且没有一个再现Dlk 1 Sul-pat无效小鼠的任何方面。因此，Dlk 1表达对于β细胞、生长激素细胞和内皮细胞的正常发育不是必需的，并且负责Dlk 1无效表型的组织仍有待鉴定。Dlk 1flox小鼠将继续为进一步研究Dlk 1的功能提供重要工具。
Numerous studies have implicated Delta-like 1 (DLK1), a transmembrane protein that shares homology with Notch ligands, in embryonic growth and differentiation. Dlk1 expression is widespread, though not ubiquitous, during early development, but is confined to a few specific cell types in adults. Adult Dlk1-expressing tissues include the Insulin-producing β-cells of the pancreas and the Growth hormone-producing somatotrophs of the pituitary gland. Previously generated Dlk1 null mice (Dlk1Sul-pat), display a partially penetrant neonatal lethality and a complex pattern of developmental and adult phenotypes. Here we describe the generation of a conditional Dlk1 mouse line (Dlk1flox) to facilitate cell type-specific deletion of the Dlk1 gene, providing a powerful system to explore each aspect of the Dlk1 null phenotype. Four tissue-specific Cre mouse lines were used to produce individual Dlk1 deletions in pancreatic β-cells, pituitary somatotrophs and the endothelial cells of the embryo and placenta, key candidates for the Dlk1 phenotype. Contrary to expectations, all of these conditional mice were fully viable, and none recapitulated any aspect of the Dlk1Sul-pat null mice. Dlk1 expression is therefore not essential for the normal development of β-cells, somatotrophs and endothelial cells, and the tissues responsible for the Dlk1 null phenotype remain to be identified. Dlk1flox mice will continue to provide an important tool for further research into the function of Dlk1.
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