Disruption of Mbd5 in mice causes neuronal functional deficits and neurobehavioral abnormalities consistent with 2q23.1 microdeletion syndrome

Vladimir Camarena, Lei Cao, Clemer Abad, Alexander Abrams, Yaima Toledo, Kimi Araki, Masatake Araki, Katherina Walz, Juan Young

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

2q23.1 microdeletion syndrome is characterized by intellectual disability, motor delay, autistic-like behaviors, and a distinctive craniofacial phenotype. All patients carry a partial or total deletion of methyl-CpG-binding domain protein 5 (MBD5), suggesting that haploinsufficiency of this gene is responsible for the phenotype. To confirm this hypothesis and to examine the role of MBD5 in vivo, we have generated and characterized an Mbd5 gene-trap mouse model. Our study indicates that the Mbd5+/GT mouse model recapitulates most of the hallmark phenotypes observed in 2q23.1 deletion carriers including abnormal social behavior, cognitive impairment, and motor and craniofacial abnormalities. In addition, neuronal cultures uncovered a deficiency in neurite outgrowth. These findings support a causal role of MBD5 in 2q23.1 microdeletion syndrome and suggest a role for MBD5 in neuronal processes. The Mbd5+/GT mouse model will advance our understanding of the abnormal brain development underlying the emergence of 2q23.1 deletion-associated behavioral and cognitive symptoms.

Original languageEnglish
Pages (from-to)1003-1015
Number of pages13
JournalEMBO Molecular Medicine
Volume6
Issue number8
DOIs
StatePublished - Jan 1 2014

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Carrier Proteins
Phenotype
Craniofacial Abnormalities
Haploinsufficiency
Behavioral Symptoms
Neurobehavioral Manifestations
Social Behavior
Intellectual Disability
Genes
Methyl CpG Binding Domain
Brain

Keywords

  • Autistic disorder
  • Intellectual disability
  • MBD5
  • Mouse model

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Disruption of Mbd5 in mice causes neuronal functional deficits and neurobehavioral abnormalities consistent with 2q23.1 microdeletion syndrome. / Camarena, Vladimir; Cao, Lei; Abad, Clemer; Abrams, Alexander; Toledo, Yaima; Araki, Kimi; Araki, Masatake; Walz, Katherina; Young, Juan.

In: EMBO Molecular Medicine, Vol. 6, No. 8, 01.01.2014, p. 1003-1015.

Research output: Contribution to journalArticle

Camarena, Vladimir ; Cao, Lei ; Abad, Clemer ; Abrams, Alexander ; Toledo, Yaima ; Araki, Kimi ; Araki, Masatake ; Walz, Katherina ; Young, Juan. / Disruption of Mbd5 in mice causes neuronal functional deficits and neurobehavioral abnormalities consistent with 2q23.1 microdeletion syndrome. In: EMBO Molecular Medicine. 2014 ; Vol. 6, No. 8. pp. 1003-1015.
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