Autism-Associated Mutations in L-Type Ca2+ Channels

Project: Research project

Project Details


Autism Spectrum Disorders (ASDs) are characterized by problems with social engagement and communication, as well as inappropriate restrictive and repetitive behaviors. It has been reported that as many as 1 in 70 children have been diagnosed with autism; therefore it represents a major health problem that also profoundly impacts a sizeable number of military families. It is known that ASDs have a strong genetic heritability component, but only in a small proportion of cases has the genetic basis been identified, and there is large heterogeneity in the genetic causes. Recently several mutations were identified in individuals with ASDs in genes that code for important Ca2+ channels. These ion channels are known to affect neuronal and synaptic development, and therefore are likely causal to autism diagnosed in these patients. More specifically, because these mutations are known to cause a gain-of-function phenotype, increasing Ca2+ influx through the channel, they provide a unique opportunity to model the disorder in a mouse and establish a “molecules to behavior” understanding of how brain circuits are functionally altered in ASDs. The two partnering laboratories have collaborated to create a novel mutant mouse with the human mutation engineered into the genome. The mice display several aberrant repetitive and social behaviors that are correlates of the altered behaviors in the human disorder. Therefore these mice are potentially valuable models for understanding the alterations in brain activity that underlie ASDs. In this proposal we will use these mice to determine the extent of the alteration in synapses, neural circuits and behavior and ask the following three questions: 1) how does the mutation in this ion channel affect the development of neurons in a region of the brain known to be important for habit? 2) what are the alterations in naturalistic behaviors in these mice that correlate with the symptoms of ASDs, and can we detect this by probing activity of
Effective start/end date9/30/189/29/21


  • U.S. Army Medical Research and Materiel Command (W81XWH1810778)


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