Transgenic complementation of MeCP2 deficiency

Phenotypic rescue of Mecp2-null mice by isoform-specific transgenes

Bredford Kerr, Jessica Soto C, Mauricio Saez, Alexander Abrams, Katherina Walz, Juan Young

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Rett syndrome (RTT) is a disorder that affects patients ability to communicate, move and behave. RTT patients are characterized by impaired language, stereotypic behaviors, frequent seizures, ataxia and sleep disturbances, with the onset of symptoms occurring after a period of seemingly normal development. RTT is caused by mutations in methyl-CpG binding protein 2 (MECP2), an X-chromosome gene encoding for MeCP2, a protein that regulates gene expression. MECP2 generates two alternative splice variants encoding two protein isoforms that differ only in the N-terminus. Although no functional differences have been identified for these splice variants, it has been suggested that the RTT phenotype may occur in the presence of a functional MeCP2-e2 protein. This suggests that the two isoforms might be functionally distinct. Supporting this notion, the two variants show regional and age-related differences in transcript abundance. Here, we show that transgenic expression of either the MeCP2-e1 or MeCP2-e2 splice variant results in prevention of development of RTT-like phenotypic manifestations in a mouse model lacking Mecp2. Our results indicate that the two MeCP2 splice variants can substitute for each other and fulfill the basic functions of MeCP2 in the mouse brain.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalEuropean Journal of Human Genetics
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Rett Syndrome
Methyl-CpG-Binding Protein 2
Transgenes
Protein Isoforms
X-Linked Genes
Aptitude
Ataxia
Sleep
Seizures
Language
Phenotype
Gene Expression
Mutation
Brain

Keywords

  • alternative splicing
  • MeCP2
  • mouse model
  • Rett syndrome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Transgenic complementation of MeCP2 deficiency : Phenotypic rescue of Mecp2-null mice by isoform-specific transgenes. / Kerr, Bredford; Soto C, Jessica; Saez, Mauricio; Abrams, Alexander; Walz, Katherina; Young, Juan.

In: European Journal of Human Genetics, Vol. 20, No. 1, 01.01.2012, p. 69-76.

Research output: Contribution to journalArticle

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