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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

Synaptic pathophysiology of 16p11.2 model mice

Principal Investigator

Principal Investigator

Bear, Mark

Description

Description

Many single-gene disorders linked to autism affect proteins that modulate the translation of messenger RNA into proteins that function at synapses, the junctions between neurons. A few examples are FMRP in fragile X syndrome, TSC1 and TSC2 in tuberous sclerosis complex and PTEN in Cowden syndrome. This led Mark Bear at the Massachusetts Institute of Technology and Raymond Kelleher at Massachusetts General Hospital to propose that ‘troubled translation’ is a core pathophysiological mechanism underlying autism spectrum disorders. This hypothesis is supported by studies of mice lacking FMRP (modeling fragile X syndrome) or mice in which one copy of TSC2 is deleted (modeling tuberous sclerosis complex). The basal rate of protein synthesis is altered in both of these model mice. However, the defect can be rectified through genetic or pharmacological treatment, which ameliorates synaptic function and corrects behavioral abnormalities. A microdeletion at human chromosome 16p11.2 is one of the most common copy number variations in autism spectrum disorders. A mouse model of this microdeletion (the chr7qF3-deficient mouse) shows behavioral phenotypes similar to some behavioral abnormalities and comorbidities associated with autism. However, the pathophysiological and biochemical mechanisms underlying these behavioral phenotypes remain unexplored. Bear and his research team aim to test whether the 16p11.2 model mice share some pathophysiology with mice lacking FMRP. If their hypothesis is correct, treatment strategies being developed for fragile X syndrome could be adopted for treating autism.

Funder

Funder

Simons Foundation

Fiscal Year Funding

Fiscal Year Funding

0

Current Award Period

Current Award Period

2012-2015

Strategic Plan Question

Strategic Plan Question

Question 4: Which Treatments And Interventions Will Help?

Strategic Plan Objective

Strategic Plan Objective

Green dot: Objective has greater than or equal to the recommended funding. 4SB. Standardize and validate at least 20 model systems (e.g., cellular and/or animal) that replicate features of ASD and will allow identification of specific molecular targets or neural circuits amenable to existing or new interventions by 2012. IACC Recommended Budget: $75,000,000 over 5 years.

Project Link

Project Link

Synaptic pathophysiology of 16p11.2 model mice (External web link)

Institution

Institution

Massachusetts Institute of Technology

State/Country

State/Country

Massachusetts

Project Number

Project Number

240559

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Synaptic pathophysiology of 16p11.2 model mice | 125000 | 2012 | 240559
Synaptic pathophysiology of 16p11.2 model mice | 250000 | 2013 | 240559
Synaptic pathophysiology of 16p11.2 model mice | 125000 | 2014 | 240559

 
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