HIGH-THROUGHPUT SCEENS FOR ASSESSING TASTE SENSITIVITY

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Humans suffer from a variety of taste disorders that impair their ability to acquire essential nutrients, regulate secretion of digestive enzymes, and enjoy one of life's simple pleasures-- eating. As there are few effective therapies for these disorders, the impending comprehensive analysis of the mouse genome offers great promise for helping fill this void. The ability of taste geneticists to identify genetically-based alterations in murine taste sensitivity has been impeded by the absence of a high-throughput screening protocol. As a result, most taste geneticists are forced to use an extremely low- throughput and interpretively limited procedure called 2-bottle preference testing. Over the last decade, taste psychophysicists have developed a high-throughput procedure for assessing taste sensitivity in rats, called brief-access taste testing. In this procedure, animals are provided with access to a single taste stimulus during brief (e.g., 10 sec) trials, and licking responses are measured with an automated gustometer. Using this device, one can present several taste stimuli (e.g., different concentrations of sucrose) during a 30-min test session in a randomized order, derive a robust concentration-response function, and be relatively confident that the licking responses are under orosensory control and not confounded by postingestive effects of the taste stimulus. We have successfully applied this methodology to study taste function in rats, and we propose here to adapt this reliable, easy-to-use, and high-throughput procedure to mice. To this end, a secondary screen will be developed for testing wild-type and mutant C57BL/6 mice. Because this screen will be conducted with an expansive array of concentrations of each taste stimulus (quinine, NaCl, and sucrose), it will be able to detect gross and subtle alterations in taste sensitivity in either direction. One the basis of the knowledge gained through the development of the secondary screen, critical concentrations will be chosen for a primary screen to provide a relatively quick assessment of taste sensitivity. Outliers identified with the primary screen can be subjected to the secondary screen for confirmation. A normative data-base for both screens will be established and made available to the scientific community. The assay procedures developed will be applicable by a single laboratory technician with limited experience.