[An experimental study on congenital foot deformity--with reference to a local disturbance in the limb bud using the...

Experimental studies on abnormal developments in mammalian embryos have been limited by an inaccessibility to the embryo for surgical manipulations. Here we have developed the exo utero survival method proposed by Muneoka et al. in 1986 to produce models of various hindlimb anomalies by cauterizing a portion of the hindlimb bud of the mouse embryo. A total of 500 mice were used. The treatment was performed on time-pregnant JCL/ICR mice at 10.5 to 12.5 days of gestation (plug day = day 0). Polydactyly occurred in the group treated with pre-axial cauterization at 10.5 to 11.0 days of gestation, and oligodactyly at 10.5 to 12.5 days of gestation. A same insult resulted in different deformities depending on the time of cauterization. Immediately after the cauterization, there was a cloudy area in the limb bud, but at 15 minutes to one hour later, it developed into a necrotic focus surrounded by hemorrhaging and hematoma. The duration of the existence of this hematoma was various. The hematoma occurred just beneath the mesenchymal tissue in the peripheral venous sinus and moved proximally at 24 to 48 hours after the cauterization, in the group treated after 11.5 days of gestation (not seen in the 12.5 days group). This fact was considered to support the progress zone and positional value theory proposed by Summerbell et al. in 1973. From this study, it was concluded that the occurrence of foot deformities such as polydactyly, oligodactyly and cleft foot would have been determined by the site, severity and time of the local insult as well as by the recoverability of the mesenchymal tissue.