Guy, Jacky

Hendrich, Brian

Holmes, Megan

Martin, Joanne E

Bird, Adrian P

5

2005-03-17T12:49:26Z

2005-03-17T12:49:26Z

2001-03

Rett syndrome (RTT) is an inherited neurodevelopmental disorder of females that occurs once in 10,000–15,000 births1,2. Affected females develop normally for 6–18 months, but then lose voluntary movements, including speech and hand skills. Most RTT patients are heterozygous for mutations in the Xlinked gene MECP2 (refs. 3–12), encoding a protein that binds to methylated sites in genomic DNA and facilitates gene silencing13– 17. Previous work with Mecp2-null embryonic stem cells indicated that MeCP2 is essential for mouse embryogenesis18. Here we generate mice lacking Mecp2 using Cre-loxP technology. Both Mecp2-null mice and mice in which Mecp2 was deleted in brain showed severe neurological symptoms at approximately six weeks of age. Compensation for absence of MeCP2 in other tissues by MeCP1 (refs. 19,20) was not apparent in genetic or biochemical tests. After several months, heterozygous female mice also showed behavioral symptoms. The overlapping delay before symptom onset in humans and mice, despite their profoundly different rates of development, raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2.

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Guy J, Hendrich B, Holmes M, Martin JE, Bird A, NATURE GENETICS, 27 (3): 322-326 MAR 2001

http://genetics.nature.com

http://hdl.handle.net/1842/727

en

Nature Publishing Group

Mouse

Mecp2-null

Mutation

neurological

symptoms

Rett syndrome

A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome

Article