Roberts C W, Shutter J R, Korsmeyer S J
Howard Hughes Medical Institute, St Louis, Missouri 63110.
Nature. 1994 Apr 21;368(6473):747-9. doi: 10.1038/368747a0.
Many homeobox genes are clustered in a linear array along a chromosome, reflecting their ordered expression along the anterior-posterior axis of the embryo. Expression patterns as well as grafting, ectopic expression and loss-of-function experiments suggest that the Hox genes encode a combinatorial system of positional specification along that axis. In contrast, the function of orphan homeobox genes located at sites outside the four mammalian Hox clusters is less well understood. To assess the functional role of the orphan homeobox gene Hox11, we have generated Hox11-deficient mice through gene targeting. Hox11-/- mice have no spleen, but otherwise appear normal. Hox11 is normally expressed in the splenic anlage arising from the splanchnic mesoderm. Hox11-/- embryos have no cellular organization at the site of splenic development but all other splanchnic derivatives develop normally. Hox11 controls the genesis of a single organ, providing new insight into the genetic regulation of morphogenesis.
许多同源异型盒基因沿染色体呈线性排列成簇，这反映了它们沿胚胎前后轴的有序表达。表达模式以及移植、异位表达和功能丧失实验表明，Hox基因编码了沿该轴的位置特异性组合系统。相比之下，位于四个哺乳动物Hox簇之外位点的孤儿同源异型盒基因的功能则了解较少。为了评估孤儿同源异型盒基因Hox11的功能作用，我们通过基因打靶产生了Hox11缺陷型小鼠。Hox11-/-小鼠没有脾脏，但其他方面看起来正常。Hox11通常在内脏中胚层产生的脾原基中表达。Hox11-/-胚胎在脾脏发育部位没有细胞组织，但所有其他内脏衍生物发育正常。Hox11控制单个器官的发生，为形态发生的遗传调控提供了新的见解。
