Behavioural neuroscienceBehavioral and anatomical abnormalities in Mecp2 mutant mice: A model for Rett syndrome
Section snippets
Subjects
Mecp21lox mice were generated as described previously (Chen et al., 2001). Two female founder mice heterozygous for the Mecp21lox null allele were obtained from Dr. R. Jaenisch (Massachusetts Institute of Technology, Cambridge, MA, USA) and used to establish a colony of Mecp21lox animals in the Department of Biological Sciences, Wellesley College. These heterozygous females of mixed genetic background (primarily BALB/C with some 129 and C57BL/6) were mated to wildtype C57BL/6J males; the
Males
Mnull mice appeared normal at birth and relatively normal when very young but could be identified occasionally by an altered gait as early as 4 weeks of age and by a significantly reduced body weight by 5 weeks of age. The body weight of Mnulls (n=21) was about half that of Mwts (n=19) (13.4±0.82 and 21.0±1.00 g respectively) [t(38)=46.9, P<0.001]. In all males, body tremors and shaking paws were noted by 5 weeks of age, and piloerection and periods of labored breathing as early as 6 weeks.
Motor deficits are associated with reductions in striatal volume
We have characterized mice with a deletion of Mecp2. Mnulls, with a mutated copy of the Mecp2 gene on their single X chromosome and no functional Mecp2 protein (Chen et al., 2001), exhibit severe motor deficits compared with wildtype males based on observations of stereotypies, abnormalities in gait and grip strength, reduced motor coordination, reduced dark cycle locomotor activity, and severely impaired swim performance. Many of these motoric abnormalities are observable by 5 weeks of age.
Conclusions
The Mecp2 mutant mice described, both here and in other studies, exhibit a phenotype that is less severe than RTT. For example, Mnull mice survive to early adulthood, and Fheteros survive to middle-age, in contrast to human RTT reports in which males only survive a year or two past birth and females survive to early adulthood (Schneider and Glaze, 2002). These differences in the effects of Mecp2 deletions in mice versus humans could result from differences in MeCP2 function in the two species,
Acknowledgments
We thank Dr. Rudolf Jaenisch for providing the founder mice for our colony, Dr. Mark Baxter for discussing these data and reading the manuscript, and Kristen Washington for setting up the automated contextual fear conditioning equipment. We also thank Olive Mwerziwa, Shoshana Maxwell, Mimi Gay-Antaki and Kathryn Swann for support with some of the experiments, and Pat Carey and Ginny Quinan for excellent animal care. Financial support for this project was provided from the following sources:
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