Quantitative trait loci associated with short-term intake of sucrose, saccharin and quinine solutions in laboratory mice.

The goal of this study was simultaneously to map two genetic loci which, collectively, have a large effect on intake of sucrose, saccharin and quinine solutions in mice. These loci had been previously identified using long-term measurements with the traditional two-bottle test, but the present study used a short-term, one-bottle test. Intake of distilled water, 100 mM sucrose, 10 mM sodium saccharin and 1.1 mM quinine HCl over 6 h was measured on two occasions from a non-deprived group of 61 male and 72 female F2 mice derived from a cross of the C57BL/6J and DBA/2J mouse strains and used to detect quantitative trait loci (QTL). DNA from each animal was typed for polymorphisms in anonymous microsatellite markers on mouse chromosomes 4 and 6. Saccharin and sucrose relevant QTL were detected on distal chromosome 4 and a quinine relevant QTL was detected on medial/distal chromosome 6 in the region of Prp. The location of these QTL and the proportion of phenotypic variance they accounted for were similar to those arrived at following previous determinations using the two-bottle test. Measurement stability for the three gustatory phenotypes was high, product-moment correlation coefficients between first and second determinations varying between approximately 0.80 for sucrose and saccharin and 0.73 for quinine. QTL parameters assessed independently for first and second presentations of sucrose and saccharin were stable, but the location of the quinine QTL differed between presentations. The present experiment illustrates the utility of a 6 h fluid intake test in the mapping of Sac and Qui loci. The short duration of the test provides a simple means of measuring variation in gustatory processes and the discovery that these loci influence short-term as well as long-term fluid intake extends understanding of the mechanism of gene action.

Genotyping new BXD recombinant inbred mouse strains and comparison of BXD and consensus maps.

Nine additional BXD recombinant inbred (RI) strains have been developed from the F2 cross of C57BL/6J and DBA/2J mouse strains. A tenth line stopped breeding in the F12 generation. F20 generation breeding pairs from the nine surviving strains and an F12 pair from the extinct line were genotyped at 319 genetic markers (primarily microsatellites) spanning most of the genome. Where typing data were lacking, the established set of 26 BXD strains also were genotyped at these same loci. The availability of these additional nine strains enhances the value of the BXD RI set for analysis of complex phenotypic traits. The proportion of loci still segregating at the F20 generation was found to closely approximate expectation, suggesting that selection favoring the retention of heterozygosity is not a strong factor. However, the number of crossovers between adjacent markers was frequently less than predicted from consensus map distances. A significant deficiency of recombinants was observed on Chrs 3, 4, 14, and X. On Chr 14, the estimated cumulative BXD map distance between the most proximal and distal markers was only 30.2 cM, compared with a distance of 60.0 cM in the consensus map. On the X Chr, the estimated and predicted cumulative distances were 38.8 and 69.5 cM, respectively. Over all chromosomes, the BXD RI map is 14.5% shorter than predicted from the consensus map. It is suggested that distances in some of the consensus maps are inflated. Alternatively, recombinant genotypes could be selected against during inbreeding owing to allelic interactions affecting fitness. The latter interpretation implies that relatively strong intrachromosomal epistasis is common.

Measuring gustatory variation in mice: a short-term fluid-intake test.

A short-term fluid-intake test is described which is directed at the study of individual variation in gustation in laboratory mice. To avoid position preferences associated with two-bottle tests, single graduated cylinders are used to present the solution. Intake of water and solutions is recorded for a 6-h period beginning 3 h prior to the dark phase of the light cycle. The timing of data collection ensures a stable baseline of fluid intake because it coincides with the period in which mice begin to drink. Food and water are available ad lib. at all other times so the test avoids the water restriction that is often used in gustatory studies. We report normative data on ten commonly used inbred strains for sucrose (100 mM), saccharin (10 mM), quinine (1.1 mM), HCI (1 and 3 mM). NaCl (320 mM), and monosodium glutamate (150 mM). Strain differences were pronounced for all tastants. Concurrent measures of food and fluid intake by C57BL/6J and DBA/2J mice demonstrated that the short-term reduction of fluid intake resulting from 6-h quinine administration, which was restricted to C57BL/6J mice, was associated with a minor reduction in food intake during the 6-h test and had no statistically significant effect on food or fluid intake during the 18-h post-test period or during a 6-h period the next day. The absence of large-scale or persistent nonspecific effects supports the use of the paradigm for screening of multiple solutions on the same animals. The reliability of the test is supported by positive correlations between repeated measurements of the same solution across substantial time intervals. Its ease of use, substantial reliability, and avoidance of water restriction make the test a very useful addition to screening tools in the field of gustation research.