With $736,000 in grants from FRAXA Research Foundation over 1998-2007, Dr. Robert Bauchwitz at Columbia University developed transgenic mouse models of Fragile X syndrome, using them to evaluate a range of experimental treatments. Results published.
We have created 15 FMR1 transgenic mouse lines. These mice lack the normal mouse FMR1 gene, but have various portions of the human X chromosome spanning the FMR1 gene inserted into their genome. Our goal was to produce a viable FMR1 sequence for use in human gene therapy for Fragile X syndrome.
One of the challenges of gene therapy is to introduce a new gene (transgene) into cells in such a way that it functions precisely like the normal gene, producing the right amount of its protein product, FMRP, at the right time and in the right cells. We aim to find the smallest piece of DNA (the FMR1 gene and regulatory sequences) necessary for the gene to function properly. Our transgenic mice have given us important information on the acceptable and necessary dose of FMRP which can be present in mice in order to restore function without causing toxicity.
We also performed extensive molecular and cognitive analysis of the original mouse model for Fragile X, the FMR1 knockout. We assessed the effects of a range of pharmacologic agents on intelligence, seizures, and other symptoms of Fragile X in these mice.