Project Detail
Interagency Autism Coordinating Committee (IACC) logo
Office of Autism Research Coordination (OARC) logo

The transcription factor PLZF: A possible genetic link between immune dysfunction and autism  

Systemic abnormalities of immune system function in patients with autism spectrum disorders (ASD) have been noted for more than 35 years. Indeed, disrupted immune system function has been proposed as a causative factor of ASD. In this Concept Award application, we propose that disrupted immune function might be correlative, but not causative of ASD. Rather, we propose that there might be a gene mutation in common. Such a gene would have important functions both for the development and/or function of the immune system as well as important functions for the development and/or function of the brain. Disruption of the function of such a gene would, therefore, independently affect both systems. We recently discovered that the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF) is critical for the function of several cell types that are part of the innate immune system. PLZF is also expressed in the brain, where it has been proposed to influence forebrain organization. Importantly, forebrain abnormalities have been noted in children with autism. We will explore the possibility that mutation of PLZF represents a commonality between immune system disruption and altered brain functions associated with ASD. A two-tier approach will be carried out. First, mice that have the PLZF gene disrupted by gene targeting will be studied for behavior abnormalities. Both PLZF deficient and haploinsufficient mice will be examined. Second, databases of human genetic variations associated with ASD will be explored to determine if allelic variations of PLZF can be correlated with ASD. Project Status
ONGOING

2010

Funder Department of Defense
Fiscal Year Funding $0.00
Current Award Period 2010-2011
Project Number AR093531
Principal Investigator Sant'Angelo, Derek
Received ARRA Funding? No
Strategic Plan Question Question 3: What Caused This To Happen And Can This Be Prevented? (Causes)
Subcategory Genetic Risk Factors
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 3LB. Identify genetic risk factors in at least 50% of people with ASD by 2014. IACC Recommended Budget: $33,900,000 over 6 years.
Federal or Private? Federal
Institution Memorial Sloan-Kettering Cancer Center
State/Country New York
Web Link 1 The transcription factor PLZF: A possible genetic link between immune dysfunction and autism (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
New! History/Related Projects The transcription factor PLZF: A possible genetic link between immune dysfunction and autism | $142,113.00 | 2009 | AR093531