Animal models of intellectual disability: towards a translational approach

Abstract

Intellectual disability is a prevalent form of cognitive impairment, affecting 2–3% of the general population. It is a daunting societal problem characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social and practical adaptive skills. Intellectual disability is a clinically important disorder for which the etiology and pathogenesis are still poorly understood. Moreover, although tremendous progress has been made, pharmacological intervention is still currently non-existent and therapeutic strategies remain limited. Studies in humans have a very limited capacity to explain basic mechanisms of this condition. In this sense, animal models have been invaluable in intellectual disability investigation. Certainly, a great deal of the knowledge that has improved our understanding of several pathologies has derived from appropriate animal models. Moreover, to improve human health, scientific discoveries must be translated into practical applications. Translational research specifically aims at taking basic scientific discoveries and best practices to benefit the lives of people in our communities. In this context, the challenge that basic science research needs to meet is to make use of a comparative approach to benefit the most from what each animal model can tell us. Intellectual disability results from many different genetic and environmental insults. Taken together, the present review will describe several animal models of potential intellectual disability risk factors.

Avances Citogenéticos y Neurobiológicos en el Síndrome de Down

“…The discovery of the human genome, especially the complete sequencing of HSA21, published in Nature (The chromosome 21 mapping and sequencing consortium, 2004) and the study of trisomic and transgenic animal models have led to considerable improvement in the knowledge of the syndrome and the consequences of this trisomy (Patterson, 2007;Scorza & Cavalheiro, 2011). For example, thanks to the sequencing of this chromosome, to date, have been identified more than 530 genes (Park, Song & Chung, 2009;Sturgeon & Gardiner, 2011).…”

“…Although the findings of these animal models are still scarce and its practical application is still limited, it may be considered that, in addition to providing basic information about the underlying etiology to DS, it is possible that their study also provide information, which on its basis early pharmacological interventions could be developed that prevent or compensate the appearance of some of the neuropsychological manifestations of DS (Gardiner, 2009;Rueda et al, 2012;Scorza andCavalheiro, 2011, Liu et al, 2011;Vacano et al, 2012) .…”

CNKSR1 gene defect can cause syndromic autosomal recessive intellectual disability

“…Animal models are invaluable and powerful systems for identification of molecular mechanisms of genetically heterogeneous diseases such as ID (Scorza & Cavalheiro, ). Among known ID genes, about 87% have a Drosophila orthologue and 76% show remarkable evolutionary conservation between humans and Drosophila (Inlow & Restifo, ; Oortveld et al, ).…”

Toward a Theory of Childhood Learning Disorders, Hyperactivity, and Aggression

“…Learning disabilities affect 2-3% of the general population [13] but are very common among children. In fact, rates have increased so greatly in recent decades that the U.S. is said to be experiencing a silent pandemic of mostly subclinical developmental neurotoxicity in which 1 in 88 children have an autism spectrum disorder (ASD) [14], about 1 in 10 are diagnosed with attention deficit hyperactivity disorder (ADHD) [15], and 1 in 6 children have a neurodevelopmental disorder involving learning disabilities, sensory deficits and/or developmental delays [16].…”