HOXA-2 MUTANT MICE EXHIBIT HOMEOTIC TRANSFORMATION OF SKELETAL ELEMENTS DERIVED FROM CRANIAL NEURAL CREST

Mice homozygous for a targeted mutation of the Hoxa-2 (Hox 1.11) gene are born with cleft palates and die within 24 hr of birth. Analysis of stained skeletons revealed that homozygous mutant animals contained m ultiple cranial skeletal defects, including a duplication of the ossif ication centers of the bones of the middle ear. Histological analysis suggested that this duplication resulted from the transformation of sk eletal elements derived from the second branchial arch into more anter ior structures, resulting in a duplication of Meckel's cartilage adjac ent to the otic capsule. Skeletal elements normally derived from the s econd arch were absent in the mutants. These data provide direct exper imental evidence for the existence of a branchial Hox code.