Studies on "Repeated Epilation" mouse mutant embryos: II. Development of limb, tail, and skin defects

The present paper reports the development of limbs, tail, and skin abnormalities in homozygous Repeated Epilation (Er/Er) mouse embryos. Defects can first be observed on day 13 and become fully expressed at 18-19 days of gestation (vaginal plug = day 1 of gestation). In 13-day-old embryos, the apical ectodermal ridge and some areas of the limb epidermis are unusually thickened. A similar hyperplasia affects the tail tip and the flank epidermis. Limb defects are located in the autopod. Both pairs of footplates are shortened and deformed; no separation occurs between the digits. Only the phalanges are involved; they may be joined together either by soft tissues or by cartilage. Hypophalangy affects the most distal phalanges. Nails are missing or poorly developed. At stage 13, the tail tip is bent over the dorsal side and becomes twisted; at later stages, the tail appears shortened. From the 14-day stage onwards, there is a progressive fusion between the limb, the body, and/or the tail epidermis. The embryological analysis of the abnormalities indicates that the thickened and rigid epidermis impedes the normal growth of the limb buds and of the tail. Our observations suggest that limb and tail defects observed in mice homozygous for the Repeated Epilation mutation may be secondary to primary changes occurring in the epidermis. Some malformations described in this paper closely resemble those observed in sm/sm (syndactylism) and pf (pupoid fetus) mouse embryos.