A partial loss of function allele of Methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome

Rodney C. Samaco, John D. Fryer, Jun Ren, Sharyl Fyffe, Hsiao Tuan Chao, Yaling Sun, John J. Greer, Huda Y. Zoghbi, Jeffrey L. Neul

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Rett Syndrome, an X-linked dominant neurodevelopmental disorder characterized by regression of language and hand use, is primarily caused by mutations in methyl-CpG-binding protein 2 (MECP2). Loss of function mutations in MECP2 are also found in other neurodevelopmental disorders such as autism, Angelman-like syndrome and non-specific mental retardation. Furthermore, duplication of the MECP2 genomic region results in mental retardation with speech and social problems. The common features of human neurodevelopmental disorders caused by the loss or increase of MeCP2 function suggest that even modest alterations of MeCP2 protein levels result in neurodevelopmental problems. To determine whether a small reduction in MeCP2 level has phenotypic consequences, we characterized a conditional mouse allele of Mecp2 that expresses 50% of the wild-type level of MeCP2. Upon careful behavioral analysis, mice that harbor this allele display a spectrum of abnormalities such as learning and motor deficits, decreased anxiety, altered social behavior and nest building, decreased pain recognition and disrupted breathing patterns. These results indicate that precise control of MeCP2 is critical for normal behavior and predict that human neurodevelopmental disorders will result from a subtle reduction in MeCP2 expression.

Original languageEnglish (US)
Pages (from-to)1718-1727
Number of pages10
JournalHuman Molecular Genetics
Volume17
Issue number12
DOIs
StatePublished - Jun 15 2008
Externally publishedYes

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Methyl-CpG-Binding Protein 2
Alleles
Intellectual Disability
Angelman Syndrome
Rett Syndrome
Mutation
Social Behavior
Social Problems
Autistic Disorder
Respiration
Language
Anxiety
Hand
Learning
Pain
Neurodevelopmental Disorders

ASJC Scopus subject areas

  • Genetics

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A partial loss of function allele of Methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome. / Samaco, Rodney C.; Fryer, John D.; Ren, Jun; Fyffe, Sharyl; Chao, Hsiao Tuan; Sun, Yaling; Greer, John J.; Zoghbi, Huda Y.; Neul, Jeffrey L.

In: Human Molecular Genetics, Vol. 17, No. 12, 15.06.2008, p. 1718-1727.

Research output: Contribution to journalArticle

Samaco, RC, Fryer, JD, Ren, J, Fyffe, S, Chao, HT, Sun, Y, Greer, JJ, Zoghbi, HY & Neul, JL 2008, 'A partial loss of function allele of Methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome', Human Molecular Genetics, vol. 17, no. 12, pp. 1718-1727. https://doi.org/10.1093/hmg/ddn062
Samaco, Rodney C. ; Fryer, John D. ; Ren, Jun ; Fyffe, Sharyl ; Chao, Hsiao Tuan ; Sun, Yaling ; Greer, John J. ; Zoghbi, Huda Y. ; Neul, Jeffrey L. / A partial loss of function allele of Methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome. In: Human Molecular Genetics. 2008 ; Vol. 17, No. 12. pp. 1718-1727.
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