ULNALESS (UI), A REGULATORY MUTATION INDUCING BOTH LOSS-OF-FUNCTION AND GAIN-OF-FUNCTION OF POSTERIOR HOXD GENES

Ulnaless (Ul), an X-ray-induced dominant mutation in mice, severely di srupts development of forearms and forelegs. The mutation maps on chro mosome 2, tightly linked to the HoxD complex, a cluster of regulatory genes required for proper morphogenesis, In particular, 5'-located (po sterior) Hoxd genes are involved in limb development and combined muta tions within these genes result in severe alterations in appendicular skeleton. We have used several engineered alleles of the HoxD complex to genetically assess the potential linkage between these two loci. We present evidence indicating that Ulnaless is allelic to Hoxd genes. I mportant modifications in the expression patterns of the posterior Hox d-12 and Hoxd-13 genes at the Ul locus suggest that Ul is a regulatory mutation that interferes with a control mechanism shared by multiple genes to coordinate Hoxd function during limb morphogenesis.