Brandeis has a long and rich history of neurogenetics in invertebrate model organisms, but only in the last two years, have we begun to begin to take full advantage of existing transgenic mouse strains and develop new ones ourselves. Prior mammalian work in the Nelson, Turrigiano, Birren and Lisman laboratories has been primarily conducted in rats. Thanks to establishment of the Mouse/Virus Core facility powerful new knockout and transgenic approaches in mice are now part of the research program in each of these laboratories, and these state-of-the-art approaches have engendered new collaborations between Brandeis faculty. For example, Birren and Sengupta are studying signaling associated with the transcription factor Arx in worms and mice, and they have begun work on a conditional knockout of Arx in mice. The Nelson lab has generated new transgenic lines which allow labeling and manipulation of specific forebrain cell types. The first characterized line labels layer 4 star-pyramid neurons in primary sensory cortices. It will enhance a collaborative project with Turrigiano on the molecular basis of changing forms of synaptic plasticity in layer 4 of visual cortex. The new mice have been made using lentiviral transgenesis and reflect the facilities newly developed capability to creat and harvest lentiviral vectors for brain transfection and transgenesis. In order to optimize delivery of lentivirus to delicate tissues we proposed to purchase a Burliegh Piezo Impact Drill system. Newer additions to the Brandeis faculty will also make use of the facility. Katz is adapting his rat multielectrode recording techniques to mice and will collaborate in multiple projects with Birren, Nelson and Turrigiano on in vivo analyses of transgenic mouse models. Paradis will join the faculty in January 2008;she will use the facility to make knockout mice important for analyzing molecules that are critical regulators of glutamatergic and GABAergic synapse development in the mammalian CNS. These include class 4 Semaphorins, which she identified in a largescale RNAi screen 1. Continued support of the facility would permit these investigators to obtain sufficient preliminary results to seek additional NINDS funding.
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