Neuronal nicotinic acetylcholine (cholinergic) receptors (nAChRs) are expressed throughout the brain as well as in the autonomic ganglia. Starting in the mid-1980's multiple neuronal nAChR subunit genes have been identified, cloned and sequenced. Today, we know of a minimum of 11 different subunits that are expressed in mammals, and 9 of these subunits are expressed in the mouse brain. It is believed that neuronal nAChRs are pentameric ligand-gated ion channels that are similar to the well-characterized muscle-type nAChR. Tremendous progress has been made in understanding these receptors using expression systems. For example, studies done in Xenopus oocytes and cell lines indicate that altering the subunit composition of the nAChRs results in tremendous changes in the physiological and pharmacological properties of these receptors. Less is known about the naturally occurring receptors. Questions that are of current interest include: Where are the nAChRs expressed in the brain; What is the subunit composition of the brain nAChRs; What role do these receptors play in synaptic transmission; What role do they play in modulating brain function (behavior), and What is their role in modulating components of the nicotine addiction process? One tool that shows incredible promise for answering these questions is the null mutant and knockin mouse. Over the last few years nAChR subunit null mutants and knockin mice have been made in several laboratories. We have been given many of these mutant animals and more have been promised to us. These animals will be used in several funded research projects. This P30 grant has been submitted to provide support for what is the world's most complete collection of nAChR transgenic mice. Support will allow us to do studies that would otherwise be nearly impossible (given the financial support currently available) such as breeding the mice on multiple genetic backgrounds and breeding double mutants. We hope that this resource will, ultimately, be made available to other researchers in the nAChR field.
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