title: Induced chromosome deletions cause hypersociability and other features of Williams-Beuren syndrome in mice.
abstract: The neurodevelopmental disorder Williams-Beuren syndrome is caused by spontaneous approximately 1.5 Mb deletions comprising 25 genes on human chromosome 7q11.23. To functionally dissect the deletion and identify dosage-sensitive genes, we created two half-deletions of the conserved syntenic region on mouse chromosome 5G2. Proximal deletion (PD) mice lack Gtf2i to Limk1, distal deletion (DD) mice lack Limk1 to Fkbp6, and the double heterozygotes (D/P) model the complete human deletion. Gene transcript levels in brain are generally consistent with gene dosage. Increased sociability and acoustic startle response are associated with PD, and cognitive defects with DD. Both PD and D/P males are growth-retarded, while skulls are shortened and brains are smaller in DD and D/P. Lateral ventricle (LV) volumes are reduced, and neuronal cell density in the somatosensory cortex is increased, in PD and D/P. Motor skills are most impaired in D/P. Together, these partial deletion mice replicate crucial aspects of the human disorder and serve to identify genes and gene networks contributing to the neural substrates of complex behaviours and behavioural disorders.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Hong Hua
authors.initials: HH
authors.lastname: Li
authors.forename: Madhuri
authors.initials: M
authors.lastname: Roy
authors.forename: Unsal
authors.initials: U
authors.lastname: Kuscuoglu
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Spencer
authors.forename: Birgit
authors.initials: B
authors.lastname: Halm
authors.forename: Katharine C
authors.initials: KC
authors.lastname: Harrison
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Bayle
authors.forename: Alessandra
authors.initials: A
authors.lastname: Splendore
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Meltzer
authors.forename: Elena
authors.initials: E
authors.lastname: Wright
authors.forename: Richard
authors.initials: R
authors.lastname: Paylor
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.forename: Uta
authors.initials: U
authors.lastname: Francke
mesh_terms: D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000473:pathology; D002872:Chromosome Deletion; D003071:Cognition; D003213:Conditioning, Psychological; D003238:Connective Tissue / Q000473:pathology; D005239:Fear; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009929:Organ Size; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000002:abnormalities; D012919:Social Behavior; D018980:Williams Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology