Learning and sexual deficiencies in transgenic mice carrying a chimeric vasoactive intestinal peptide gene
- 47 Downloads
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 EntriesVIP diphtheria toxin, polyoma promoter genetic manipulation VIP transgenic animals learning and memory, sexual behavior
Unable to display preview. Download preview PDF.
- Csillag A., Zilles K., Schleicher A., and Hajos F. (1992) Matching localization of immunoreactive VIP and VIP receptor in the visual cortex.Neurosci. Soc. Abs. 18, 1451.Google Scholar
- Gozes I., Hill J. M., Mervis R. F., Fridkin M., and Brenneman D. E. (1990) VIP antagonist produces neuronal damage and retardation of behavioral development in neonatal rats.Neurosci. Soc. Abs. 16, 1292.Google Scholar
- Gozes I., McCune S. K., Jacobson L., Warren D., Moody T. W., Fridkin M., and Brenneman D. E. (1991a) An antagonist to vasoactive intestinal peptide: effects on cellular functions in the central nervous system.J. Pharmacol. Exp. Therap. 257, 959–966.Google Scholar
- Heinrich G., Gros P., and Habener J. F. (1984) Glucagon gene sequence.J. Biol. Chem.,259, 14,082–14,087.Google Scholar
- Magistretti P. J., Morrison J. H., Shoemaker W. J., Sapin V., and Bloom F. E. (1981) Vasoactive intestinal polypeptide induces glycogenolysis in mouse cortical slices: a possible regulatory mechanism for the local control of energy metabolism.Proc. Natl. Acad. Sci. USA 78, 6535–6539.PubMedCrossRefGoogle Scholar
- Ottesen B., Wagener G., Virag R., and Fahrenkrug J. (1984) Penile erection: possible role for vasoactive intestinal polypeptide.Br. Med. J. 288, 9–11.Google Scholar
- Tybulewicz V. L. J., Tremblay M. L., Lamarca M. E., Willemsen R., Stubblefield B. K., Winfield S., Zablocka B., Sidransky E., Martin B. M., Huang S. P., Mintzer K. A., Westphal H., Mulligan R. C., and Ginns E. I. (1992) Animal model of Gaucher’s diseae from targeted disruption of the mouse glucocerebrosidase gene.Nature 357, 407–410.PubMedCrossRefGoogle Scholar