Williams-Beuren syndrome (WBS) is among the most compelling genetic disorders of human development and behavior and is due to a recurring deletion of about 1,55-1,83 Mb containing 25-28 genes in chromosome band 7q11.23 [
1,
2]. Individuals with WBS manifest characteristic craniofacial dysmorphic features, cardiovascular problems, mild to moderate mental retardation and mild growth retardation [
3]. The behavioral and cognitive profile of WBS individuals is characterized by relatively proficient language and face-processing skills, but serious impairments in visuo-spatial and numerical abilities. Personality traits include overfriendliness and charismatic speech. Hyperacusis or algiacusis is an almost constant feature. The roots of the mental and cognitive aspects of WBS probably lie in disruption of normal neurodevelopment, because brain morphology and neural organization are abnormal [
4]. A firm pathogenic mechanism has been established for the cardiovascular problems that are known to be caused by haploinsufficiency for the elastin gene [
5]. Additional candidates for involvement in several aspects of the WBS phenotype have been proposed on the basis of clinical-molecular correlations in a few patients with partial phenotypes and smaller deletions. Two members of the
GTF2I gene family,
GTF2I and
GTF2IRD1, highly expressed during development and in normal neuronal tissues, are strong candidates for the craniofacial and some neurobehavioral features of WBS [
6‐
9]. Homozygous loss of either the
Gtf2i or
Gtf2ird1 function in mice provided additional evidence for the involvement of both genes in the craniofacial and cognitive phenotype. Mice with a heterozygous deletion of exons 2-4 of
Gtf2ird1 are less aggressive, more sociable and possibly less anxious [
10‐
12]. However, any phenotype identified in a model of total deletion can potentially be assigned to the distal or the proximal half of the deletion indicating that loss of genes in both half-deletions may contribute to the phenotype [
13]. Mouse models that resemble the WBS genetically and phenotypically are crucial to understand the roles haploinsufficient genes play in development, cognition and behavior. A great deal of information about possible functions of TFII-I has been obtained recently [
9,
12,
14]. However, despite all these advances, the specific contribution of these genes to the phenotype and the underlying pathogenic mechanisms of the disease are not yet fully understood. Here, we have studied the
in vivo effects of an in frame deletion of exon 2 of
Gtf2i. The phenotypic characterization of this mouse model confirms that any alteration in the correct function of TFII-I contribute to important features displayed by WBS patients such as the craniofacial abnormalities and some neurobehavioral features including hyperacusis.