Hox genes and mesomelic dysplasia

In this sixth and final lesson, the function and regulation of HoxD genes during limb development are discussed, starting with the 1990 production of the Ulnaless (Ul) mutant mouse strain, a mutation causing severe mesomelic dysplasia. This almost complete reduction of mid-limb bones, accompanied by severe deformities, is also observed in human patients, expressed as an autosomal dominant trait. Characterization of this Ulnaless inversion containing the murine HoxD cluster is gradually leading to an understanding of the mechanisms involved in the production of these alterations, revealing fundamental points affecting the control of gene expression and function in the limbs. These studies in mice are leading to the formulation of an inclusive explanatory scheme to explain the molecular causes of cases of familial mesomelic dysplasia associated with human chromosome 2q31, the locus containing this same cluster of HoxD genes in humans.