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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

Rat knockout models of ASD

Principal Investigator

Principal Investigator

Paylor, Rich

Description

Description

The advent of transgenic technologies has revolutionized behavioral science. While mouse genetic models have been invaluable for studying underlying neurobiological mechanisms, mouse behavioral analyses have often been challenging. Until very recently, the use of rats as potential genetic models for disorders of the human CNS has not been realized because of the inability to readily manipulate their genome. Scientists at SAGE Labs have now developed a strategy for creating knockout (KO) rats and under a novel partnership with Autism Speaks are generating ones with mutation in ASD susceptibility genes. Currently rat models with mutations in Fmr1, Mecp2, Neurexin 1, Neuroligin 3, and MGluR5 have been created and additional lines are being generated. The investigators have developed a test battery for rats to study ASD-related behavioral responses. The battery includes assessments for ultrasonic communication, repetitive/perseverative responding, and social interactions. In addition, assays for anxiety-like responses and cognition, as well as a number of important control assays for activity and olfactory function are employed. The investigators have completed evaluations of Fmr1 and Neuroligin 3, and are in the process of completing studies with Mecp2, Neurexin 1 and mGluR5. This study evaluates three additional lines of rats on the standard test battery. The three lines include Shank3 and Shank2. Completed studies with Fmr1 and Neuroligin 3 have demonstrated a number of ASD-like traits including reduced play behavior and increased perseverative chewing. Research findings clearly indicate that rat KO lines will be an important research tool for future ASD research and the evaluation of potential therapeutic targets. Therefore, evaluating additional rat KO lines for ASD-like traits on a consistent behavioral-battery platform is necessary and important to continue to increase the number of genetically-modified rat models for scientists interested in ASD.

Funder

Funder

Autism Speaks

Fiscal Year Funding

Fiscal Year Funding

100441

Current Award Period

Current Award Period

2012-2013

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

Rat knockout models of ASD (External web link)

Institution

Institution

Baylor College of Medicine

State/Country

State/Country

Texas

Project Number

Project Number

8413

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Rat knockout models of ASD | 0 | 2013 | 8413
Rat knockout models of ASD | 0 | 2014 | 8413

 
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