Growth defects and impaired cognitive-behavioral abilities in mice with knockout for Eif4h, a gene located in the mouse homolog of the Williams-Beuren syndrome critical region

Am J Pathol. 2012 Mar;180(3):1121-1135. doi: 10.1016/j.ajpath.2011.12.008. Epub 2012 Jan 9.


Protein synthesis is a tightly regulated, energy-consuming process. The control of mRNA translation into protein is fundamentally important for the fine-tuning of gene expression; additionally, precise translational control plays a critical role in many cellular processes, including development, cellular growth, proliferation, differentiation, synaptic plasticity, memory, and learning. Eukaryotic translation initiation factor 4h (Eif4h) encodes a protein involved in the process of protein synthesis, at the level of initiation phase. Its human homolog, WBSCR1, maps on 7q11.23, inside the 1.6 Mb region that is commonly deleted in patients affected by the Williams-Beuren syndrome, which is a complex neurodevelopmental disorder characterized by cardiovascular defects, cerebral dysplasias and a peculiar cognitive-behavioral profile. In this study, we generated knockout mice deficient in Eif4h. These mice displayed growth retardation with a significant reduction of body weight that began from the first week of postnatal development. Neuroanatomical profiling results generated by magnetic resonance imaging analysis revealed a smaller brain volume in null mice compared with controls as well as altered brain morphology, where anterior and posterior brain regions were differentially affected. The inactivation of Eif4h also led to a reduction in both the number and complexity of neurons. Behavioral studies revealed severe impairments of fear-related associative learning and memory formation. These alterations suggest that Eif4h might contribute to certain deficits associated with Williams-Beuren syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / growth & development
  • Brain / metabolism
  • Conditioning, Psychological / physiology
  • Eukaryotic Initiation Factors / deficiency*
  • Eukaryotic Initiation Factors / genetics*
  • Eukaryotic Initiation Factors / metabolism
  • Exploratory Behavior / physiology
  • Fear
  • Female
  • Gene Deletion
  • Growth Disorders / genetics*
  • Heterozygote
  • Learning Disabilities / genetics*
  • Male
  • Memory Disorders / genetics*
  • Mice
  • Mice, Knockout
  • Muscle Fatigue / genetics
  • Mutagenesis, Insertional
  • Organ Size
  • Psychomotor Performance / physiology
  • RNA, Messenger / metabolism
  • Williams Syndrome / genetics*
  • Williams Syndrome / psychology


  • EIF4H protein, human
  • Eukaryotic Initiation Factors
  • RNA, Messenger