Viral Vector-mediated Addition of the Fmr1 Gene to Fmr1 Null Mice
Fragile X syndrome is the most common form of inherited mental retardation, affecting approximately 1:6000 individuals. The syndrome arises from the silencing of the fragile X mental retardation gene (FMR1), which results in a lack of the fragile X mental retardation protein (FMRP). This protein is an RNA binding protein that influences a number of aspects of neural development and plasticity. This study pioneers the feasibility of delivering Fmr1 DNA into neurons lacking a functional copy of the gene by utilizing viral vectors. The viral particles contain coding information for the Fmr1 gene as well as a reporter gene, which serves as a marker to evaluate transduction efficiency. Previous data suggested that packing constraints and limited neurotropism of the recombinant adeno-assosiciated virus (rAAV) may affect its ability to infect hippocampal neurons in vitro. As a result, the Herpes Simplex Virus, a vector with increased neurotropism and transgene capacity, was chosen for in vivo evaluation alongside the rAAV. Preliminary results derived from histological methods performed on Fmr1 knockout tissue revealed altered levels on protein expression between the HSV-injected and non-injected hippocampi. Future experiments will determine to what extent and why changes in protein expression were observed with special focus placed upon the role of the inflammatory response.
School:
University of Illinois at Urbana-Champaign
Department:
Molecular and Cellular Biology
Research Advisor:
William T. Greenough
Department of Research Advisor:
Psychology
Year of Publication:
2005