LEARNING AND SEXUAL DEFICIENCIES IN TRANSGENIC MICE CARRYING A CHIMERIC VASOACTIVE-INTESTINAL-PEPTIDE GENE

The molecular mechanisms responsible for behavior are largely unknown. A state of the art model, paving the path from genes to behavior, is offered by transgenic animals. Candidate molecules are classic neurope ptides, such as vasoactive intestinal peptide (VIP). Transgenic mice h arboring a chimeric VIP gene driven by the polyoma promoter were produ ced. Behavioral studies revealed learning impairment and prolonged ret ardation in memory acquisition in the genetically altered animals. Fur thermore, reduced performance was observed when the male transgenic mi ce were tested for sexual activity in the presence of receptive female s. Surprisingly, radioimmunoassays showed an approx 20% decrease in th e VIP content of the transgenic mice brains. To directly assess geneti cally reduced VIP content as a cause for learning impairment, transgen ic mice carrying diphtheria toxin-encoding sequences driven by the rat VIP promoter were created. These animals had reduced brain VIP and ex hibited deficiencies in learning abilities, strongly supporting an imp ortant neurobiological function for VIP in vivo.