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.

Growth defects and impaired cognitivebehavioral abilities in mice with knockout for Eif4h, a gene located in the mouse homolog of the Williams-Beuren syndrome critical region / S. Capossela, L. Muzio, A. Bertolo, V. Bianchi, G. Dati, L. Chaabane, C. Godi, L.S. Politi, S. Biffo, P. D'Adamo, A. Mallamaci, M. Pannese. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 180:3(2012), pp. 1121-1135.

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

S. Biffo;
2012

Abstract

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.
animal cell; animal experiment; animal model; animal tissue; article; associative memory; behavior disorder; brain cortex; brain nerve cell; brain region; brain size; cognitive defect; computer assisted tomography; conditioning; controlled study; embryo; emotion; exploratory behavior; fear; female; gene expression; gene inactivation; gene location; growth retardation; hyperactivity; infertility; learning disorder; male; memory disorder; motor coordination; mouse; muscle fatigue; neuroanatomy; neuroimaging; nonhuman; nuclear magnetic resonance imaging; polysome; postnatal development; priority journal; protein synthesis; spatial memory; state dependent learning; weight reduction; Williams Beuren syndrome
Settore BIO/06 - Anatomia Comparata e Citologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/256001
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