An Adult Brain-Specific Mouse Model of Neuronal TSC Inactivation

Completed

Kelleher, Raymond

Massachusetts General Hospital

$120,000.00

2 years

Pilot

Boston

MA

United States

2007

http://www.massgeneral.org

City: 
Boston
State/Province: 
MA
State/Province Full: 
Massachusetts
Country: 
United States

Whilst the genetic basis of autism is complex, several childhood disorders characterized by mental retardation are due to mutations in single genes and are associated with a high incidence of autistic features. Understanding the impact of mutations of such genes on brain development and function promises to provide important insights into the causes of autism, and may help identify potential therapeutic strategies. Tuberous sclerosis complex (TSC) and fragile X syndrome (FXS) are known risk factors for autism and recently, the gene products that are mutated in TSC and FXS have been shown to be involved in the regulation of protein synthesis which is important for memory formation. Thus it is possible that aberrant regulation of protein synthesis in brain cells may contribute to the development of autism. In an experimental mouse model, in which the TSC gene has been genetically modified over the entire life span (including embryonic development), abnormalities in brain development are seen which are similar to those people with TSC. This approach does not distinguish the critical period (i.e. pre- or post-natally) in which the abnormal TSC gene exerts its effect. The present study will use a TSC mouse model to examine the relationship between brain abnormalities and behavioral and cognitive impairments and will specifically address what happens when the abnormality in the TSC gene is induced only in the post-natal period (i.e. after birth and thereby bypassing any effects on brain development). What this means for people with autism: This study has the capability to provide insight into gene defects, and consequently defects in protein synthesis, which occur specifically at postnatal stages. This approach will provide inroads toward a therapeutic strategy in TSC with broader implications for therapies in autism.