Mice homozygous for the recessive mutation swaying (SW) are characterized by ataxia and hypertonia, attributed to the malformation of anterior regions of the cerebellum. We show that SW is a deletion of a single base pair from the proto-oncogene Wnf-1. The deletion is predicted to cause premature termination of translation, eliminating thecarboxy-terminal half of the Writ-1 protein. Histological examination shows that SW is phenotypically identical to a previously described writ-1 mutation introduced into mice by gene targeting. Although both mutations in Wnf-1 disrupt primarily the development of the anterior cerebellum, they also exhibit a variability in expressivity such that rostrally adjacent structures in the midbrain and caudally adjacent structures in the posterior cerebellum can also be affected. introduction

Processes as seemingly different as insect segmentation and vertebrate neural development require the activity of genes from the Wntfamily (Nusse et al., 1991). This family of genes is found in genera throughout the animal kingdom, including Caenorhabditis (Kamb et al., 1989), Drosophila (Cabrera et al., 1987; Rijsewijk et al., 1987), Xenopus (Noordermeer et al., 1989), and Homo (Van’t Veer et al., 1984). Members of the Writ family are related by sequence similarity and share a signal sequence motif, potential glycosylation sites, and a highly conserved array of 21 cysteine residues concentrated toward the carboxyl half of the protein. In Drosophila, the Writ gene family is represented by the segment polarity gene wingless (wg), which is required for pattern formation within each embryonic segmental unit as well as for the normal development of wing and leg imaginal disks (Morata and Lawrence, 1977; Baker, 1987; Martinez-Arias et al., 1988). The wg gene acts in a non-cell autonomous fashion, presumably via a secreted protein that stimulates the growth and/or differentiation of adjacent cells (Morata and Lawrence, 1977; Van den Heuvel et al., 1989). In mice there are at least ten expressed members of this family (McMahon and McMahon, 1989; Gavin et al., 1990; Roelink et al., 1990; Roelink and Nusse, 1991). The protein coded by the mu-