Deletion of the mental retardation gene Gdi1 impairs associative memory and alters social behavior in mice

Patrizia D'Adamo, Hans Welzl, Stavros Papadimitriou, Marina Raffaele Di Barletta, Cecilia Tiveron, Laura Tatangelo, Laura Pozzi, Paul F. Chapman, Simon G. Knevett, Mark F. Ramsay, Flavia Valtorta, Chiara Leoni, Andrea Menegon, David P. Wolfer, Hans Peter Lipp, Daniela Toniolo

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Abstract

Non-specific mental retardation (NSMR) is a common human disorder characterized by mental handicap as the only clinical symptom. Among the recently identified MR genes is GDI1, which encodes αGdi, one of the proteins controlling the activity of the small GTPases of the Rab family in vesicle fusion and intracellular trafficking. We report the cognitive and behavioral characterization of mice carrying a deletion of Gdi1. The Gdi1-deficient mice are fertile and anatomically normal. They appear normal also in many tasks to assess spatial and episodic memory and emotional behavior. Gdi1-deficient mice are impaired in tasks requiring formation of short-term temporal associations, suggesting a defect in short-term memory. In addition, they show lowered aggression and altered social behavior. In mice, as in humans, lack of Gdi1 spares most central nervous system functions and preferentially impairs only a few forebrain functions required to form temporal associations. The general similarity to human mental retardation is striking, and suggests that the Gdi1 mutants may provide insights into the human defect and into the molecular mechanisms important for development of cognitive functions.

Original languageEnglish
Pages (from-to)2567-2580
Number of pages14
JournalHuman Molecular Genetics
Volume11
Issue number21
Publication statusPublished - Oct 1 2002

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ASJC Scopus subject areas

  • Genetics

Cite this

D'Adamo, P., Welzl, H., Papadimitriou, S., Di Barletta, M. R., Tiveron, C., Tatangelo, L., Pozzi, L., Chapman, P. F., Knevett, S. G., Ramsay, M. F., Valtorta, F., Leoni, C., Menegon, A., Wolfer, D. P., Lipp, H. P., & Toniolo, D. (2002). Deletion of the mental retardation gene Gdi1 impairs associative memory and alters social behavior in mice. Human Molecular Genetics, 11(21), 2567-2580.