Journal Article

Defective body-weight regulation, motor control and abnormal social interactions in <i>Mecp2</i> hypomorphic mice

Bredford Kerr, Matías Alvarez-Saavedra, Mauricio A. Sáez, Alexandra Saona and Juan I. Young

in Human Molecular Genetics

Volume 17, issue 12, pages 1707-1717
Published in print June 2008 | ISSN: 0964-6906
Published online March 2008 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddn061
Defective body-weight regulation, motor control and abnormal social interactions in Mecp2 hypomorphic mice

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MeCP2 is an abundant protein that binds to methylated cytosine residues in DNA and regulates transcription. Mutations in MECP2 cause Rett syndrome, a severe neurological disorder that affects approximately 1:10 000 females. Mice lacking MeCP2 have been generated and constitute important models of Rett syndrome. However, it is yet unclear whether certain physiological events are sensitive to a decrease, rather than a complete lack of MeCP2. Here we report that a Mecp2 floxed allele (Mecp2lox) that was generated to allow conditional mutagenesis behaves as a hypomorph and the corresponding mutant mice exhibit phenotypical alterations including body weight gain, motor abnormalities and altered social behavior. Our data reinforce the view that the central nervous system is extremely sensitive to MeCP2 expression levels and suggest that the 3′-UTR of Mecp2 might contain important elements that contribute to the regulation of its stability or processing.

Journal Article.  7509 words.  Illustrated.

Subjects: Genetics and Genomics

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