Thus, altered splicing due to the DTTTCT deletion polymorphism, such as exon skipping or intron retention, will result in a protein product that is truncated at this region and therefore lacks the important class-defining GAP function. These results, in turn, suggest that individuals carrying the deletion polymorphism have a higher BMI due to a reduction in the functional levels of brain RGS9-2. Support for the suggestion that RGS9-2 is important in regulating body-weight is provided by the finding that mice with the RGS9 gene deletion have elevated body weight and that conversely overexpressing RGS9-2 in the rat nucleus accumbens, via herpes simplex virus -mediated gene transduction, lowers body weight relative to control animals. RGS9- 2 is expressed in the vast majority of striatal medium spiny neurons, which comprise 90�C95% of the neurons in the striatum. Hence, the percentage of infected non-target cells that do not normally express RGS9-2 is small and consequently, this technique has been successfully utilized to define physiological and pathophysiological functions for RGS9-2 using both rodent and primate models. Indeed, the results presented above mirror those from previous studies, where HSV-mediated RGS9-2 over-expression in the rat striatum has been shown to produce functional responses that are opposite to those exhibited by the RGS9 knockout mice. For example, RGS9 knockout mice exhibit increased cocaine-induced locomotion, while HSV-mediated overexpression of RGS9-2 in rats dampens cocaine-induced locomotion. In addition, RGS9 knockout mice show accelerated development of drug-induced dyskinesia, while HSV-mediated overexpression of RGS9-2 in the striatum of rats and monkeys diminished intensity of druginduced dyskinesia. The specificity of RGS9-2 overexpression effects are highlighted by the parallel experiments with RGS7 and RGS11, closely related members of the R7 RGS protein family. Though RGS11 is thought to be specifically expressed in retinal bipolar neuron, the two proteins have been shown in vitro to act as BU 4061T GTPase accelerating proteins for the same G proteins. The opposite effects of RGS9-2 and RGS7 andRGS11 overexpression on body weight suggest that the effects cannot be attributed solely to the GAP function which is common to the three proteins. While we do not yet understand the mechanism for the opposing action of these proteins on body weight, it is interesting to note that R7 RGS proteins, such as RGS7, RGS9 and RGS11, can compete for their obligate binding partners. In fact, knock-out of these binding CUDC-907 partners leads to marked reduction in all R7 RGS proteins.