DEFECTIVE LIMBIC SYSTEM IN MICE LACKING THE TAILLESS GENE

The gene tailless is a member of the superfamily of genes that encode transcription factors of the ligand-activated nuclear receptor type, a nd is expressed in the invertebrate and vertebrate brain(1-4). In mice , its transcripts are restricted to the periventricular zone of the fo rebrain(4), the site of origin of neurons and glia. Here we use homolo gous recombination to generate mice that lack a functional tailless pr otein. Homozygous mutant mice are viable at birth, indicating that tai lless is not required for prenatal survival; however, adult mutant mic e show a reduction in the size of rhinencephalic and limbic structures , including the olfactory, infrarhinal and entorhinal cortex, amygdala and dentate gyrus. Both male and female mice are more aggressive than usual and females lack normal maternal instincts. These animals there fore enable a molecular approach to be taken towards understanding the genetic architecture and morphogenesis of the forebrain.