Mouse models of Rett syndrome: from behavioural phenotyping ... : Behavioural Pharmacology (original) (raw)

REVIEW ARTICLES

Mouse models of Rett syndrome: from behavioural phenotyping to preclinical evaluation of new therapeutic approaches

Sections of aBehavioural Neuroscience

bNeurotoxicology and Neuroendocrinology, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, Roma, Italy

Correspondence to Dr Giovanni Laviola, Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Margherita 299, Roma, Italy

E-mail: [email protected]

*Laura Ricceri and Bianca De Filippis have contributed equally to this study.

Received 31 March 2008 Accepted as revised 29 May 2008

Abstract

Rett syndrome (RTT) is a neurodevelopmental disorder, primarily affecting girls. RTT causes severe cognitive, social, motor and physiological impairments and no cure currently exists. The discovery of a monogenic origin for RTT and the subsequent generation of RTT mouse models provided a major breakthrough for RTT research. Although the characterization of these mutant mice is far from complete, they recapitulate several RTT symptoms. This review provides an overview of the behavioural domains so far investigated in these models, including the very few mouse data concerning the developmental course of RTT. Both clinical and animal studies support the presence of early defects and highlight the importance of probing the presymptomatic phase for both the precocious identification of biomarkers and the early assessment of potential therapies. Preclinical evaluations of pharmacological and nonpharmacological interventions so far carried out are also illustrated. In addition, genetic manipulations are reported that demonstrate rescue from the damage caused by the absence of the methyl-CpG-binding protein 2 (MeCP2) gene even at a mature stage. Given the rare occurrence of RTT cases, transnational collaborative networks are expected to provide a deeper understanding of aetiopathology and the development of new therapeutic approaches.