David B. Harder

Genetics of bitter perception in mice.

Inbred and congenic strains exhibited several patterns of relative sensitivity to bitter tastants in 48-h, two-bottle preference tests. With segregation analyses of descendents of crosses between contrasting strains, these patterns suggested at least three genetic loci influencing bitter perception. The extensively characterized Soa (sucrose octaacetate) locus underlies one pattern. Variation at this locus had pleiotropic effects on avoidance of other acetylated sugars, plus such structurally dissimilar bitter tastants as brucine, denatonium benzoate, and quinine sulfate. Unlike SOA, however, sensitivity to quinine sulfate was polygenically determined, and produced a second characteristic pattern. At least one, possibly several, additional unlinked loci contributed to quinine differences. Phenylthiocarbamide (PTC) aversion differences exemplified a third pattern. Segregation consistent with monogenic control of PTC aversion has been reported, and within segregating populations PTC aversion did not covary with SOA or quinine sulfate avoidance. Variants of the three major patterns may be useful for analysis of specific mechanisms. While both showed the SOA pattern, strychnine differences were markedly smaller than brucine (dimethoxystrychnine) differences. Likewise, a hop extract containing primarily iso-alpha acids (e.g., isohumulone) produced an SOA-like pattern, while an extract with nonisomerized alpha-acids (e.g., humulone) did not.

Single-locus control of sucrose octaacetate tasting among mice

SWR/J mice avoid sucrose octaacetate (SOA) solutions at concentrations which other inbred strains do not. This phenotypic difference has been hypothesized to result from variation at a single autosomal locus with two alleles, one dominant (Soaa, aversion) and one recessive (Soaa, blind). Data from reciprocal F1 and F2 crosses of SWR/J (taster) and C57BL/6J (nontaster) mice and from four generations of selective lineal backcrossing to the C57BL/6J strain, in two-bottle preference tests with 10−5M SOA, were used to test this monogenic model against two polygenic models. The phenotypic ratios expected in the segregating generations according to the single-locus model were consistent with the observed ratios. The ratios expected with either two-locus model were inconsistent with those found. A strain distribution pattern, also consistent with monogenic variation, was found when a set of recombinant inbred strains (SWXL/Ty) derived from SWR/J and C57L/J (nontaster) mice was similarly tested. Outbred CFW mice (inbred substrains of which had been reported by separate laboratories to be both SOA tasters and SOA nontasters) were found to be polymorphic for SOA tasting. An allele identical by descent to that in the SWR/J strain may be segregating in this (distantly) related line.

The B6.SW bilineal congenic sucrose octaacetate (SOA)-Taster mice

SWR/J inbred mice (Tasters) reliably avoid, whereas C57BL/6J inbred mice (Nontasters) are indifferent to, sucrose octaacetate (SOA) at certain concentrations. From these strains we have developed a set of bilineal congenic Taster mice. Approximately 4000 mice, from 2 isogenic and 12 segregating generations, were tested in a program designed to evaluate genetic models for SOA tasting during development of congenic strains. The criterion phenotype was avoidance or nonavoidance in preference tests of the bitter tastant SOA at concentrations of 10−4 and 10−5M. Across the 12 segregating generations, the results were consistent with Mendelian expectations for a single autosomal locus with complete dominance of the Taster phenotype. The breeding program produced 12 replicate B6.SW lines containing the taster allele on the B6-Nontaster genomic background. The congenic Taster mice may facilitate a functional analysis of the sense of taste.

Phenylthiocarbamide (PTC) preference among laboratory mice: understanding of a previously "unreplicated" report.

In two-bottle preference tests aversion to phenylthiocarbamide (PTC) develops over a period of days. Thus, as previously reported, following experience with appropriate concentrations of PTC, mice of the BALB inbred strain display an aversion in contrast to C57BL inbred mice. It is suggested that differential learning in a conditioned taste-aversion paradigm might be responsible for the phenotypic strain contrast. The difference in PTC aversion phenotype among mice could be due to differences in any mechanism contributing to differential flavor toxicosis conditioning instead of, or in addition to, strain differences in sensitivity to the sensory attributes of PTC.

Defensive burying by mice: Intraspecific genetic variation and retention

Genotypically based within-species differences in defensive burying were examined in 180 mice representing 15 inbred strains. Each mouse was tested twice in a cylindrical test chamber containing two similar prods. In the first test, one of the prods was electrified, whereas in the second test (24 h later), neither prod was. Although most strains selectively buried the shock prod in the first test (as determined by bedding-height-at-prod and position-of-highest-bedding-pile criteria), some strains did not discriminate between the shock and dummy prods and still others displayed little prod-directed bedding displacement at all (thereby resembling a heterogeneous nonshocked control group). In general, burying tended to be somewhat reduced in the second test, but strain differences in retention were observed. Factors contributory to the observed differences among strains and the need for multiple measures of burying are discussed. Collectively, these findings indicate that intraspecific genetic variation, acting at multiple burying-relevant behavioral levels, can be an important determinant of the expression of the defensive-burying response in mice.

Genotype and environment interactively determine the magnitude, directionality, and abolition of defensive burying in mice

Genotypic and environmental contributions to the defensive burying response were examined by testing four sublines of two inbred strains of mice in test chambers of three different lengths. Burying was found to be dependent on both the particular subline tested and the length of the test chamber employed. For two sublines, specific increases in the length of the test chamber resulted in the complete abolition of defensive burying. A third subline never displayed defensive burying, and the fourth buried in all three chamber-length conditions. Sex differences in burying were never observed. Rather than being viewed as a species-specific defensive reaction, it was proposed that defensive burying should more appropriately be viewed as a genotypically dependent response, the expression of which is contingent on the specific environmental context in which an aversive stimulus is encountered. Apparent conflicts in the defensive-burying literature were reconciled in accordance with this interpretation.