Induced chromosome deletions cause hypersociability and other features of Williams–Beuren syndrome in mice
| Autor: | Birgit Halm, Karl Deisseroth, Joseph H. Bayle, Feng Ding, Katharine C. Harrison, Madhuri Roy, Hong Hua Li, Unsal Kuscuoglu, Corinne M. Spencer, Uta Francke, Leslie Meltzer, Richard Paylor, Elena E. Wright, Alessandra Splendore |
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| Rok vydání: | 2009 |
| Předmět: |
Williams Syndrome
Heterozygote Heart Ventricles Motor Activity LIMK1 Biology Gene dosage Mice 03 medical and health sciences Cognition 0302 clinical medicine Neurodevelopmental disorder Conditioning Psychological medicine Animals Humans mouse models Social Behavior Gene 030304 developmental biology Genetics Regulation of gene expression 0303 health sciences neurobehavioural phenotype Reverse Transcriptase Polymerase Chain Reaction Skull Brain Chromosome Heterozygote advantage Fear Organ Size medicine.disease Phenotype Gene Expression Regulation Connective Tissue Molecular Medicine Williams syndrome Chromosome Deletion Closeup microdeletion 030217 neurology & neurosurgery |
| Zdroj: | EMBO Molecular Medicine |
| ISSN: | 1757-4684 1757-4676 |
| DOI: | 10.1002/emmm.200900003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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