Intracisternal Gtf2i Gene Therapy Ameliorates Deficits in Cognition and Synaptic Plasticity of a Mouse Model of Williams-Beuren Syndrome.

ABSTRACT: Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a heterozygous deletion of 26-28 genes at chromosome band 7q11.23. Haploinsufficiency at GTF2I has been shown to play a major role in the neurobehavioral phenotype. By characterizing the neuronal architecture in four animal models with intragenic, partial, and complete deletions of the WBS critical interval (ΔGtf2i(+/-), ΔGtf2i( -/-), PD, and CD), we clarify the involvement of Gtf2i in neurocognitive features. All mutant mice showed hypersociability, impaired motor learning and coordination, and altered anxiety-like behavior. Dendritic length was decreased in the CA1 of ΔGtf2i(+/-), ΔGtf2i ( -/-), and CD mice. Spine density was reduced, and spines were shorter in ΔGtf2i ( -/-), PD, and CD mice. Overexpression of Pik3

SUBMITTER: Borralleras C 

PROVIDER: S-EPMC4817950 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature