CRANIOFACIAL ABNORMALITIES IN HOMOZYGOUS SMALL EYE (SEY SEY) EMBRYOS AND NEWBORN MICE/

The Small eye (Sey) gene in the mouse is lethal in the homozygous stat e. It is located on chromosome 2, is a mutation in the Pax-6 gene, and is genetically homologous with the human aniridia 2 (AN2) gene mutati on. Numerous studies over the last few years, using genetic and molecu lar biological approaches, have investigated both the location of the gene as well as its possible mode of action. In the homozygous state, the primary defect appears to be limited to the failure of differentia tion of the presumptive lens and nasal placodes. Such mice therefore d isplay a characteristic phenotype; they possess neither eyes nor any n asal derivatives. Their heterozygous (Sey/+) and normal(+/+) littermat es may be distinguished before birth only by a detailed examination of their eyes. Few detailed morphological/histological studies have been undertaken to date in the Sey/Sey embryos and newborn, and in the pre sent study we describe a variety of craniofacial abnormalities that ha ve not previously been reported. We observed, with one exception, dela yed closure of the palate, and the presence in 80 % of mice of an abno rmal complement of upper incisor teeth, so that 35 % possessed 1 super numerary tooth while 45 % possessed 2 supernumerary teeth. In these mi ce, a total of either 3 or 4, rather than the normal complement of 2, upper incisor teeth were present. Possibly the most unexpected finding , however, was the presence of a median cartilaginous rod-like structu re which protruded between the 2 maxillae to give the Alizarin red S a nd Alcian blue-stained 'cleared' skulls of the newborn mice a characte ristic 'unicorn-like' appearance. While this structure appeared to be a rostral. extension of the chondrocranium, its exact derivation is un clear.