Substantial evidence suggests that chromosomal abnormalities contribute to the risk of autism. The duplication of human chromosome 15q11-13 is known to be the most frequent cytogenetic abnormality in autism. We have modeled this genetic change in mice by using chromosome engineering to generate a 6.3 Mb duplication of the conserved linkage group on mouse chromosome 7. Mice with a paternal duplication display poor social interaction, behavioral inflexibility, abnormal ultrasonic vocalizations, and correlates of anxiety. An increased MBII52 snoRNA within the duplicated region, affecting the serotonin 2c receptor (5-HT2cR), correlates with altered intracellular Ca(2+) responses elicited by a 5-HT2cR agonist in neurons of mice with a paternal duplication. This chromosome-engineered mouse model for autism seems to replicate various aspects of human autistic phenotypes and validates the relevance of the human chromosome abnormality. This model will facilitate forward genetics of developmental brain disorders and serve as an invaluable tool for therapeutic development.
Pubmed ID: 19563756 RIS Download
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NEURON is a simulation environment for modeling individual neurons and networks of neurons. It provides tools for conveniently building, managing, and using models in a way that is numerically sound and computationally efficient. It is particularly well-suited to problems that are closely linked to experimental data, especially those that involve cells with complex anatomical and biophysical properties. NEURON has benefited from judicious revision and selective enhancement, guided by feedback from the growing number of neuroscientists who have used it to incorporate empirically-based modeling into their research strategies. NEURON's computational engine employs special algorithms that achieve high efficiency by exploiting the structure of the equations that describe neuronal properties. It has functions that are tailored for conveniently controlling simulations, and presenting the results of real neurophysiological problems graphically in ways that are quickly and intuitively grasped. Instead of forcing users to reformulate their conceptual models to fit the requirements of a general purpose simulator, NEURON is designed to let them deal directly with familiar neuroscience concepts. Consequently, users can think in terms of the biophysical properties of membrane and cytoplasm, the branched architecture of neurons, and the effects of synaptic communication between cells. * helps users focus on important biological issues rather than purely computational concerns * has a convenient user interface * has a user-extendable library of biophysical mechanisms * has many enhancements for efficient network modeling * offers customizable initialization and simulation flow control * is widely used in neuroscience research by experimentalists and theoreticians * is well-documented and actively supported * is free, open source, and runs on (almost) everything
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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