Open AccessInduced chromosome deletions cause hypersociability and other features of Williams–Beuren syndrome in mice
Author(s) -
Li Hong Hua,
Roy Madhuri,
Kuscuoglu Unsal,
Spencer Corinne M.,
Halm Birgit,
Harrison Katharine C.,
Bayle Joseph H.,
Splendore Alessandra,
Ding Feng,
Meltzer Leslie A.,
Wright Elena,
Paylor Richard,
Deisseroth Karl,
Francke Uta
Publication year - 2009
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 - 10.1002/emmm.200900003
Subject(s) - genetics , biology , chromosome , chromosome 21 , williams syndrome , gene , neuroscience , cognition
Abstract The neurodevelopmental disorder Williams–Beuren syndrome is caused by spontaneous ∼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.