Harrison K A, Thaler J, Pfaff S L, Gu H, Kehrl J H
Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Genet. 1999 Sep;23(1):71-5. doi: 10.1038/12674.
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. This developmental process depends upon an integrated network of transcription factors. Gene targeting experiments have revealed critical roles for Pdx1, Isl1, Pax4, Pax6 and Nkx2-2 (refs 3,4,5,6,7, 8,9,10). The homeobox gene HLXB9 (encoding HB9) is prominently expressed in adult human pancreas, 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 beta-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.
在大多数哺乳动物中，胰腺从前肠内胚层发育而来，形成腹侧和背侧芽。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。这个发育过程依赖于一个转录因子的整合网络。基因靶向实验已经揭示了Pdx1、Isl1、Pax4、Pax6和Nkx2-2的关键作用（参考文献3、4、5、6、7、8、9、10）。同源盒基因HLXB9（编码HB9）在成年人类胰腺中显著表达，但其在胰腺发育和功能中的作用尚不清楚。为了便于对其进行研究，我们分离出了小鼠HLXB9的直系同源基因Hlxb9。在小鼠发育过程中，胰腺的背侧和腹侧芽以及胰岛中的成熟β细胞表达Hlxb9。在Hlxb9基因敲除突变的同源小鼠中，胰腺的背叶无法发育。残留的Hlxb9-/-胰腺有小的胰岛，产生胰岛素的β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是正常胰腺发育和功能的关键。
