Article

Journal of Molecular Neuroscience

, Volume 4, Issue 3, pp 185-193

Learning and sexual deficiencies in transgenic mice carrying a chimeric vasoactive intestinal peptide gene

  • Illana GozesAffiliated withDepartment of Chemical Pathology, Sackler School of Medicine, Tel Aviv University
  • , John GlowaAffiliated withBiopsychology Unit, Clinical Neuroendocrinology Branch, NIMH
  • , Douglas E. BrennemanAffiliated withSection of Developmental and Molecular Pharmarcology, LDN, NICHD
  • , Susan K. McCuneAffiliated withSection of Developmental and Molecular Pharmarcology, LDN, NICHD
  • , Eric LeeAffiliated withLaboratory of Mammalian Genes and Development, NICHD, NIH
  • , Heiner WestphalAffiliated withLaboratory of Mammalian Genes and Development, NICHD, NIH

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Abstract

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 neuropeptides, such as vasoactive intestinal peptide (VIP). Transgenic mice harboring a chimeric VIP gene driven by the polyoma promoter were produced. Behavioral studies revealed learning impairment and prolonged retardation in memory acquisition in the genetically altered animals. Furthermore, reduced performance was observed when the male transgenic mice were tested for sexual activity in the presence of receptive females. Surprisingly, radioimmunoassays showed an approx 20% decrease in the VIP content of the transgenic mice brains. To directly assess genetically reduced VIP content as a cause for learning impairment, transgenic mice carrying diphtheria toxia-encoding sequences driven by the rat VIP promoter were created. These animals had reduced brain VIP and exhibited deficiencies in learning abilities, strongly supporting an important neurobiological function for VIP in vivo.

Index Entries

VIP diphtheria toxin, polyoma promoter genetic manipulation VIP transgenic animals learning and memory, sexual behavior