Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis

Matías Alvarez-Saavedra, Mauricio A. Sáez, Dongcheul Kang, Huda Y. Zoghbi, Juan I. Young

Resultado de la investigación: Article

49 Citas (Scopus)

Resumen

Rett syndrome (RTT), a leading cause of mental retardation with autistic features in females, is caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). RTT is characterized by a diverse set of neurological features that includes cognitive, motor, behavioral and autonomic disturbances. The diverse features suggest that specific neurons contribute to particular phenotypes and raise the question whether restoring MeCP2 function in a cell-specific manner will rescue some of the phenotypes seen in RTT. To address this, we generated transgenic mice expressing inducible MeCP2 under the control of the brain-specific promoters calcium/calmodulin-dependent protein kinase II (CamKII) or neuron-specific enolase (Eno2) and bred them onto mouse models lacking functional MeCP2. Expression of normal MeCP2 in either CamKII or Eno2 distribution was unable to prevent the appearance of most of the phenotypes of the RTT mouse models. These results suggest that most RTT phenotypes are caused either by disruption of complex neural networks involving neurons throughout the brain or by disruption of the function of specific neurons outside of the broad CamKII or Eno2 distribution.

Idioma originalEnglish
Páginas (desde-hasta)2315-2325
Número de páginas11
PublicaciónHuman Molecular Genetics
Volumen16
N.º19
DOI
EstadoPublished - 1 oct 2007

Huella dactilar

Methyl-CpG-Binding Protein 2
Rett Syndrome
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Phenotype
Neurons
Calcium-Calmodulin-Dependent Protein Kinases
Phosphopyruvate Hydratase
Brain
Intellectual Disability
Transgenic Mice
Mouse Mecp2 protein
Mutation
Genes

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Medicine(all)
  • Genetics(clinical)

Citar esto

Alvarez-Saavedra, Matías ; Sáez, Mauricio A. ; Kang, Dongcheul ; Zoghbi, Huda Y. ; Young, Juan I. / Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis. En: Human Molecular Genetics. 2007 ; Vol. 16, N.º 19. pp. 2315-2325.
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abstract = "Rett syndrome (RTT), a leading cause of mental retardation with autistic features in females, is caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). RTT is characterized by a diverse set of neurological features that includes cognitive, motor, behavioral and autonomic disturbances. The diverse features suggest that specific neurons contribute to particular phenotypes and raise the question whether restoring MeCP2 function in a cell-specific manner will rescue some of the phenotypes seen in RTT. To address this, we generated transgenic mice expressing inducible MeCP2 under the control of the brain-specific promoters calcium/calmodulin-dependent protein kinase II (CamKII) or neuron-specific enolase (Eno2) and bred them onto mouse models lacking functional MeCP2. Expression of normal MeCP2 in either CamKII or Eno2 distribution was unable to prevent the appearance of most of the phenotypes of the RTT mouse models. These results suggest that most RTT phenotypes are caused either by disruption of complex neural networks involving neurons throughout the brain or by disruption of the function of specific neurons outside of the broad CamKII or Eno2 distribution.",
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Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis. / Alvarez-Saavedra, Matías; Sáez, Mauricio A.; Kang, Dongcheul; Zoghbi, Huda Y.; Young, Juan I.

En: Human Molecular Genetics, Vol. 16, N.º 19, 01.10.2007, p. 2315-2325.

Resultado de la investigación: Article

TY - JOUR

T1 - Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis

AU - Alvarez-Saavedra, Matías

AU - Sáez, Mauricio A.

AU - Kang, Dongcheul

AU - Zoghbi, Huda Y.

AU - Young, Juan I.

PY - 2007/10/1

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N2 - Rett syndrome (RTT), a leading cause of mental retardation with autistic features in females, is caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). RTT is characterized by a diverse set of neurological features that includes cognitive, motor, behavioral and autonomic disturbances. The diverse features suggest that specific neurons contribute to particular phenotypes and raise the question whether restoring MeCP2 function in a cell-specific manner will rescue some of the phenotypes seen in RTT. To address this, we generated transgenic mice expressing inducible MeCP2 under the control of the brain-specific promoters calcium/calmodulin-dependent protein kinase II (CamKII) or neuron-specific enolase (Eno2) and bred them onto mouse models lacking functional MeCP2. Expression of normal MeCP2 in either CamKII or Eno2 distribution was unable to prevent the appearance of most of the phenotypes of the RTT mouse models. These results suggest that most RTT phenotypes are caused either by disruption of complex neural networks involving neurons throughout the brain or by disruption of the function of specific neurons outside of the broad CamKII or Eno2 distribution.

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