We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Targeted delivery of an Mecp2 transgene to forebrain neurons improves the behavior of female Mecp2-deficient mice.
- Authors
Jugloff, Denis G M; Vandamme, Katrina; Logan, Richard; Visanji, Naomi P; Brotchie, Jonathan M; Eubanks, James H
- Abstract
Rett syndrome is an X-linked neurological condition affecting almost exclusively girls that is caused by mutations of the MECP2 gene. Recent studies have shown that transgenic delivery of MeCP2 function to Mecp2-deficient male mice can improve their Rett-like behavior. However, as the brain of a Rett girl contains a mosaic of MeCP2 expressing and non-expressing neurons, and the over-expression of MeCP2 in neurons can induce a severe progressive neurological phenotype, testing whether functional rescue can be achieved by gene re-introduction strategies in a female model of Rett syndrome is warranted. To address this, we generated transgenic mice expressing an epitope-tagged Mecp2 transgene in forebrain neurons. These mice over-express MeCP2 protein at about 1.6 times normal levels in cortex and develop impaired motor behavior by 9-12 months of age. To test whether forebrain-targeted MeCP2 restoration would improve behavior in female Mecp2(-/+) mice, we crossed these transgenics with Mecp2(-/+) mice and examined the behavioral properties of the female rescue mice for 1 year. These assessments revealed that the diminished rearing activity, impaired mobility and the diminished locomotive activity of female Mecp2(-/+) mice were restored to wild-type levels in the rescue mice. These results show that improvement of Rett-like behavior can be achieved in Mecp2(-/+) females by targeted gene re-introduction without inducing deficits relating to MeCP2 over-expression.
- Publication
Human molecular genetics, 2008, Vol 17, Issue 10, p1386
- ISSN
1460-2083
- Publication type
Journal Article
- DOI
10.1093/hmg/ddn026