title: The methyl binding domain containing protein MBD5 is a transcriptional regulator responsible for 2q23.1 deletion syndrome.
abstract: 2Iq23.1 microdeletion syndrome is a recently described rare disease that includes intellectual disability, motor delay, autistic-like behaviors, and craniofacial abnormalities. Dosage insufficiency of the methyl-CpG-binding domain protein 5 (MBD5) gene was suggested as the genetic cause, since all the described patients carry a partial or total heterozygous deletion of MBD5. We reported the generation and characterization of a mouse model with haploinsufficiency for Mbd5 that confirmed this hypothesis. As in human 2q23.1 microdeletion syndrome, the MBD5 (+/GT) mouse model exhibited abnormal social behavior, cognitive impairment, and motor and craniofacial abnormalities, supporting a causal role for MBD5 in 2q23.1 microdeletion syndrome. The use of mouse neuronal cultures uncovered a deficiency in neurite outgrowth, suggesting the participation of MBD5 in neuronal processes. The study of the MBD5 (+/GT) mouse advanced our understanding of the abnormal brain development associated with behavioral and cognitive symptoms.
authors.affiliation: Dr. John T Macdonald Foundation; Department of Human Genetics; University of Miami; FL, USA; John P. Hussman Institute for Human Genomics; University of Miami; FL, USA; Department of Medicine; Miller School of Medicine; University of Miami; FL, USA.
authors.forename: Katherina
authors.initials: K
authors.lastname: Walz
authors.affiliation: Dr. John T Macdonald Foundation; Department of Human Genetics; University of Miami; FL, USA; John P. Hussman Institute for Human Genomics; University of Miami; FL, USA.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Young
keywords: 2q23.1 microdeletion syndrome; Mbd5; autism; intellectual disabilities; mouse model; transcriptional regulator