Identifying interactions between genes and early environment in the mouse

Interactions between genetic and early environmental factors are recognized to play a critical role in modulating susceptibility to disease, particularly mental illness. In order to better understand such mechanisms at the molecular level, we have developed a screening paradigm in mice that allows us to test the ability of targeted mutations in candidate genes to modify susceptibility to the long-term effects of different maternal environment. Offspring of genetically identical F1 hybrid dams produced by reciprocal breeding of C57BL/6 and BALB/c parents show alterations in anxiety-related behavior as a consequence of their different maternal environment. Introduction of targeted mutations into these offspring via the father allows for the identification of candidate genes that alter these maternal effects. Our strategy offers several advantages over other methods to study maternal effects, including the use of genetically identical parents, the ability to identify both prenatal and postnatal effects, the straightforward introduction of mutations and its adaptability to high-throughput screening. In order to test the utility of this paradigm to screen candidate genes, we tested for gene–environment interactions involving loss of- function mutations in the serotonin 1A receptor gene. Our studies demonstrate that early gene–environment interactions can be successfully tested in the mouse. When combined with conditional gene targeting and other molecular genetic techniques available in the mouse, this approach has the potential to identify the molecular mechanisms underlying early gene– environment effects

Auditory processing in children with dyslexia

Background: it has been claimed that children with dyslexia show a general impairment in the processing of rapid auditory stimuli. However, most previous studies in this field have focused on children with language impairment or children who do not meet accepted criteria for dyslexia.Methods: in the present study, the processing of rapid non-verbal auditory stimuli (complex tones) was examined in a population-based sample of 24 children with dyslexia, 10 to 12 years of age, and a matched control group.Results: the dyslexia group showed reduced tone processing relative to the control group, with significant main effects of tone duration, inter-stimulus interval and task complexity. The deficit was not specific for temporal order errors, and could not be explained by differences in short-term memory or verbal IQ. However, correlations between tone processing and reading ability were generally low or absent.Conclusion: although a general processing deficit for rapid auditory stimuli in dyslexia was confirmed, its relevance for reading problems and hence for treatment programmes for dyslexia is questioned.<br/