The human autosomal dominant disorder oculodentodigital dysplasia (ODDD) is characterized by developmental anomalies of the limbs, teeth, face and eyes. Mutations in the gap junction protein alpha 1 gene (GJA1), which encodes connexin 43 (Cx43), have recently been linked to ODDD. Now, Flenniken and colleagues describe a heterozygous mutant mouse(Gja1Jrt/+) that exhibits many of the characteristics of human ODDD (see p. 4375). The mutant mice have a point mutation in Gja1 that causes a substitution of a highly conserved amino acid (G60S) in Cx43. The researchers show that this mutant Cx43 acts in a dominant- negative manner to disrupt gap junction assembly and function in vivo and in vitro. They also describe the phenotype of the Cja1Jrt/+ mice in detail,highlighting some abnormalities not normally seen in human ODDD patients but which might cause problems as these individuals age.