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Mouse Models of Hereditary Mental Retardation

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Transgenic and Knockout Models of Neuropsychiatric Disorders

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

Abstract

This chapter describes a number of genetic mouse models of syndromic and nonsyndromic mental retardation (MR), focusing primarily on X-linked retardation models: the fragile X model, involving the fragile site mental retardation 1 gene (FMR1) the FRAXE model, involving the fragile site mental retardation 2 gene (FMR2); the Coffin-Lowry syndrome model, involving ribosomal S6 kinase 2 (RSK2); models involving GDP dissociation inhibitor (GDI)-1 mutations; the Rett syndrome model, involving the methyl-CpG-binding protein 2 (MECP2); the lacking angiotensin receptor 2 (AGTR2) model; the corpus callosum hypoplasia, mental retardation, adducted thumbs, spastic paraplegia, and hydrocephalus (CRASH) syndrome model, involving mutations of the cell adhesion molecule, L1; and models involving mutations of rho guanine nucleotide exchange factor 6 (ARHGEF6). Autosomal dominant models include neurofibromatosis type 2 (NF1) and phenylketonuria (PAH). The phenotypes of experimentally altered mouse genes mostly include relatively moderate pleiotropic changes in neuroanatomy, electrophysiology, and behavioral test scores, the latterrarely matching the severity of the human phenotype. Interpretation is hampered by a general lack of understanding the causation of mental variation, and by neglecting species-specific peculiarities of mouse neuinvaluable tools for an empirical analytical approach deciphering the complex pathways between genotype and mental phenotype, chiefly because the developmental end point is, at least for nonsyndromic human MR, always severely impaired cognition. This is not the case for mouse models generated on the basis of theoretical expectations for memory and learning.

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Authors
  1. Hans Welzl
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  2. Patrizia D’Adamo
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  3. David P. Wolfer
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  4. Hans-Peter Lipp
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Editor information

Editors and Affiliations

  1. Department of Statistics, Yeshiva University, New York, NY

    Gene S. Fisch PhD

  2. Department of Psychology, CUNY/Lehman College, New York, NY

    Gene S. Fisch PhD

  3. Wellcome Trust Centre for Human Genetics, Oxford, UK

    Jonathan Flint MD, MRCPsych

  4. Department of Psychiatry, University of Oxford, Oxford, UK

    Jonathan Flint MD, MRCPsych

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© 2006 Humana Press Inc., Totowa, NJ

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Welzl, H., D’Adamo, P., Wolfer, D.P., Lipp, HP. (2006). Mouse Models of Hereditary Mental Retardation. In: Fisch, G.S., Flint, J. (eds) Transgenic and Knockout Models of Neuropsychiatric Disorders. Contemporary Clinical Neuroscience. Humana Press. https://doi.org/10.1007/978-1-59745-058-4_6

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