HOX11 CONTROLS THE GENESIS OF THE SPLEEN

MANY homeobox genes are clustered in a linear array along a chromosome , reflecting their ordered expression along the anterior-posterior axi s of the embryo(1). Expression patterns(2,3) as well as grafting(4), e ctopic expression(5,6) and loss-of-function experiments(7-11) suggest that the Hox genes encode a combinatorial system of positional specifi cation along that axis. In contrast, the function of orphan homeobox g enes(12) located at sites outside the four mammalian Hox clusters is l ess well understood. To assess the functional role of the orphan homeo box gene Hox11, we have generated Hox11-deficient mice through gene ta rgeting. Hox11(-/-) mice have no spleen, but otherwise appear normal. Hox11 is normally expressed in the splenic anlage arising from the spl anchnic mesoderm. Hox11(-/-) embryos have no cellular organization at the site of splenic development but all other splanchnic derivatives d evelop normally. Hox11 controls the genesis of a single organ, providi ng new insight into the genetic regulation of morphogenesis.