Rett Syndrome

Neurobiology of Disease

Rett Syndrome

• 2nd most common genetic cause of Mental Retardation

• Early development normal loss of language, cognitive and motor abilities

• Single gene defect: Mecp2

• KO (Jaenisch, Bird) recapitulates disease, as does forebrain neuron selective KO.

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http://www.ncbi.nlm.nih.gov/disease/chr21-Y.html

Zohgbi, 2003

MeCP2 represses gene expression

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Cre/lox system

http://www.bioteach.ubc.ca/MolecularBiology/TargetingYourDNAWithTheCreloxSystem/

But remarkably little effect on gene expression detected in microarray study of mouse KOTudor et al. 2002

MeCP2 represses gene expression

Shabazian et al. 2002

Luikenhuis, Giacometti, Beard, Jaenisch (2004)

Fig 1.

Luikenhuis, Giacometti, Beard, Jaenisch (2004)

Fig 2.

Luikenhuis, Giacometti, Beard, Jaenisch (2004)

Fig 3.

Luikenhuis, Giacometti, Beard, Jaenisch (2004) Fig 4.

Dani et al. (2005) Fig 1.

Dani et al. (2005) Fig 2.

Dani et al. (2005)

Fig 3.

Dani et al. (2005)Fig 4.

Dani et al. (2005)Fig 5.