Targeted Disruption of L-Proline Transporter Gene by Homolgous Recombination

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Many of the most exciting technical advances in neurobiology have come from the field of genetic engineering. It is now possible to selectively "knock out" single genes and examine their effect on behavior. Knock-out mice, as they are called, have been used to probe the circuits underlying learning and memory, temperature adaptation, and many other behaviors. They provide highly selective probes for elucidating the long mysterious connection between genes and behavior. Dr. Fremeau has recently cloned the gene for a high-affinity membrane transporter for proline. The fact that these uptake systems for proline are found in selective populations of glutaminergic nerve terminals suggests that proline is a novel neurotransmitter which modifies glutaminergic transmission in some way. Since glutamate is a major transmitter in cerebral cortex and involved in mechanisms of neuroplasticity, it is obviously of great interest to determine proline's role in glutaminergic function. This NSF small grant for exploratory research (SGER) will give Dr. Fremeau the chance to use genetic engineering techniques to solve this problem. He will attempt the high-risk/high gain task of producing a knock out mouse that lacks this membrane component. If he succeeds it will be possible to determine the role that proline neurotransmission plays in the development of behavior. This is the kind of research for which the SGER was designed for there are few other funding mechanisms for supporting research that does not have a fairly assured payoff.***//