Loss of fibula in mice overexpressing Hoxc11

This study demonstrates severe malformations of the appendicular skeleton i n I-nice overexpressing Hoxc11. Consistent with the endogenous expression p attern, the most conspicuous defect in Hoxc11 overexpressing neonates is ap lasia/hypoplasia of the fibula. This is preceded at day 15.5 of embryonic d evelopment by marked reduction of chondrocyte proliferation, lack of PTHR e xpressing prehypertrophic cells, and the absence of hypertrophic and calcif ying chondrocytes. Combined with the lack of an overt phenotype in the majo rity of Hoxc11 overexpressing embryos at day 13.5, the data suggest inhibit ion of chondrocyte differentiation during the elongation phase of the fibul a bone as a primary effect of elevated Hoxc11 expression. This interpretati on is further corroborated by Hoxc11 reporter gene expression in the joint areas at embryonic day 15.5, suggesting an involvement of the periarticular perichondrium in generating the mutant phenotype. (C) 2000 Elsevier Scienc e Ireland Ltd. All rights reserved.