HOX11 CONTROLS THE GENESIS OF THE SPLEEN
HOX11 CONTROLS THE GENESIS OF THE SPLEEN
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DOI：
10.1038/368747a0
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发表时间：
1994-04-21
期刊：
影响因子：
64.8
通讯作者：
KORSMEYER, SJ
中科院分区：
文献类型：
--
作者：
ROBERTS, CWM;SHUTTER, JR;KORSMEYER, SJ
许多同源异型盒基因沿染色体沿着成线性排列，反映了它们沿胚胎前后轴沿着有序表达（1）。表达模式（2，3）以及移植（4）、异位表达（5，6）和功能丧失实验（7-11）表明，Hox基因编码沿该轴沿着定位的组合系统。相比之下，位于四个哺乳动物Hox簇之外的孤儿同源盒基因（12）的功能还不太清楚。为了评估孤儿同源盒基因Hox 11的功能作用，我们通过基因靶向产生了Hox 11缺陷小鼠。Hox 11（-/-）小鼠没有脾脏，但其他方面表现正常。Hox 11通常在源自内脏中胚层的脾原基中表达。Hox 11（-/-）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。Hox 11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。
MANY homeobox genes are clustered in a linear array along a chromosome, reflecting their ordered expression along the anterior-posterior axis of the embryo(1). Expression patterns(2,3) as well as grafting(4), ectopic expression(5,6) and loss-of-function experiments(7-11) suggest that the Hox genes encode a combinatorial system of positional specification along that axis. In contrast, the function of orphan homeobox genes(12) 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.