Postnatal loss of methyl-CpG binding protein 2 in the forebrain is sufficient to mediate behavioral aspects of Rett syndrome in mice.
BACKGROUND
Mutations in the methyl-CpG binding protein 2 (MeCP2) gene cause Rett syndrome (RTT), a neurodevelopmental disorder that is accompanied by a broad array of behavioral phenotypes, mainly affecting females. Methyl-CpG binding protein 2 is a transcriptional repressor that is widely expressed in all tissues.


METHODS
To investigate whether the postnatal loss of MeCP2 in the forebrain is sufficient to produce the behavioral phenotypes observed in RTT, we have generated conditional MeCP2 knockout mice.


RESULTS
These mice display behavioral abnormalities similar to RTT phenotypes, including hindlimb clasping, impaired motor coordination, increased anxiety, and abnormal social behavior with other mice. These mice, however, have normal locomotor activity and unimpaired context-dependent fear conditioning, suggesting that the behavioral deficits observed are the result of loss of MeCP2 function in postnatal forebrain and not the result of generalized global deficits.


CONCLUSIONS
These data highlight the important role of MeCP2 in the forebrain and suggest that even partial loss of MeCP2 expression in these brain regions is sufficient to recapitulate features of RTT.
Gemelli
Terry
T
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
Berton
Olivier
O
Nelson
Erika D
ED
Perrotti
Linda I
LI
Jaenisch
Rudolf
R
Monteggia
Lisa M
LM
D000818:Animals; D000831:Animals, Newborn; D001143:Arousal / Q000235:genetics; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D010641:Phenotype; D016548:Prosencephalon / Q000473:pathology*; D011597:Psychomotor Performance / Q000502:physiology; D015518:Rett Syndrome / Q000235:genetics* / Q000473:pathology; D012919:Social Behavior
C497392:MECP2 protein, human; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2