Open AccessDisruption of Mbd5 in mice causes neuronal functional deficits and neurobehavioral abnormalities consistent with 2q23.1 microdeletion syndrome
Author(s) -
Camarena Vladimir,
Cao Lei,
Abad Clemer,
Abrams Alexander,
Toledo Yaima,
Araki Kimi,
Araki Masatake,
Walz Katherina,
Young Juan I
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201404044
Subject(s) - haploinsufficiency , phenotype , intellectual disability , microdeletion syndrome , autism , neuroscience , biology , craniofacial , gene , genetics , psychology , developmental psychology
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 ( MBD 5 ), suggesting that haploinsufficiency of this gene is responsible for the phenotype. To confirm this hypothesis and to examine the role of MBD 5 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 MBD 5 in 2q23.1 microdeletion syndrome and suggest a role for MBD 5 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.