Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice
Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice
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DOI：
10.1038/12674
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发表时间：
1999-09-01
期刊：
影响因子：
30.8
通讯作者：
Kehrl, JH
中科院分区：
文献类型：
--
作者：
Harrison, KA;Thaler, J;Kehrl, JH
在大多数哺乳动物中，胰腺由前肠内胚层发育为腹侧和背侧芽。这些芽融合并发育成一个由内分泌、外分泌和导管成分组成的复杂器官（1,2）。这种发育过程依赖于一个完整的转录因子网络。基因靶向实验揭示了Pdx1， lsl1, Pax4， Pax6和Nkx2-2的关键作用（参考文献3-10）。同源盒基因HLXB9（编码HB9）在成人胰腺中显著表达（11），尽管其在胰腺发育和功能中的作用尚不清楚。为了便于研究，我们分离了小鼠HLXB9同源物HLXB9。在小鼠发育过程中，朗格汉斯胰岛的背侧和腹侧胰腺芽和成熟β细胞表达Hlxb9。在Hlxb9零突变的同源小鼠中，胰腺背叶不能发育。残余的Hlxb9（-/-）胰腺有小的朗格汉斯岛，产生胰岛素的p细胞数量减少。Hlxb9(-/-) β细胞表达低水平的葡萄糖转运蛋白Glut2和同源结构域因子Nkx 6-1。因此，Hlxb9是胰腺正常发育和功能的关键。
In most mammals the pancreas develops from the foregut endoderm as ventral and dorsal buds. These buds fuse and develop into a complex organ composed of endocrine, exocrine and ductal components(1,2). This developmental process depends upon an integrated network of transcription factors. Gene targeting experiments have revealed critical roles for Pdx1, lsl1, Pax4, Pax6 and Nkx2-2 (refs 3-10). The homeobox gene HLXB9 (encoding HB9) is prominently expressed in adult human pancreas(11), although its role in pancreas development and function is unknown. To facilitate its study, we isolated the mouse HLXB9 orthologue, Hlxb9. During mouse development, the dorsal and ventral pancreatic buds and mature beta-cells in the islets of Langerhans express Hlxb9. In mice homologous for a null mutation of Hlxb9, the dorsal lobe of the pancreas fails to develop. The remnant Hlxb9(-/-) pancreas has small islets of Langerhans with reduced numbers of insulin-producing p-cells. Hlxb9(-/-) beta-cells express low levels of the glucose transporter Glut2 and homeodomain factor Nkx 6-1. Thus, Hlxb9 is key to normal pancreas development and function.