Maltodextrin Acceptance and Preference in Eight Mouse Strains.

Rodents are strongly attracted to the taste(s) of maltodextrins. A first step toward discovery of the underlying genes involves identifying phenotypic differences among inbred strains of mice. To do this, we used 5-s brief-access tests and 48-h 2-bottle choice tests to survey the avidity for the maltodextrin, Maltrin M040, of mice from 8 inbred strains (129S1/SvImJ, A/J, CAST/EiJ, C57BL/6J, NOD/ShiLTJ, NZO/HlLtJ, PWK/PhJ, and WSB/EiJ). In brief-access tests, the CAST and PWK strains licked significantly less maltodextrin than equivalent concentrations of sucrose, whereas the other strains generally licked the 2 carbohydrates equally. Similarly, in 2-bottle choice tests, the CAST and PWK strains drank less 4% maltodextrin than 4% sucrose, whereas the other strains had similar intakes of these 2 solutions; the CAST and PWK strains did not differ from the C57, NOD, or NZO strains in 4% sucrose intake. In sum, we have identified strain variation in maltodextrin perception that is distinct from variation in sucrose perception. The phenotypic variation characterized here will aid in identifying genes responsible for maltodextrin acceptance. Our results identify C57 × PWK mice or NZO × CAST mice as informative crosses to produce segregating hybrids that will expose quantitative trait loci underlying maltodextrin acceptance and preference.

Normal Taste Acceptance and Preference of PANX1 Knockout Mice.

Taste compounds detected by G protein-coupled receptors on the apical surface of Type 2 taste cells initiate an intracellular molecular cascade culminating in the release of ATP. It has been suggested that this ATP release is accomplished by pannexin 1 (PANX1). However, we report here that PANX1 knockout mice do not differ from wild-type controls in response to representative taste solutions, measured using 5-s brief-access tests or 48-h two-bottle choice tests. This implies that PANX1 is unnecessary for taste detection and consequently that ATP release from Type 2 taste cells does not require PANX1.

Salty taste deficits in CALHM1 knockout mice.

Genetic ablation of calcium homeostasis modulator 1 (CALHM1), which releases adenosine triphosphate from Type 2 taste cells, severely compromises the behavioral and electrophysiological responses to tastes detected by G protein-coupled receptors, such as sweet and bitter. However, the contribution of CALHM1 to salty taste perception is less clear. Here, we evaluated several salty taste-related phenotypes of CALHM1 knockout (KO) mice and their wild-type (WT) controls: 1) In a conditioned aversion test, CALHM1 WT and KO mice had similar NaCl avoidance thresholds. 2) In two-bottle choice tests, CALHM1 WT mice showed the classic inverted U-shaped NaCl concentration-preference function but CALHM1 KO mice had a blunted peak response. 3) In brief-access tests, CALHM1 KO mice showed less avoidance than did WT mice of high concentrations of NaCl, KCl, NH(4)Cl, and sodium lactate (NaLac). Amiloride further ameliorated the NaCl avoidance of CALHM1 KO mice, so that lick rates to a mixture of 1000 mM NaCl + 10 µM amiloride were statistically indistinguishable from those to water. 4) Relative to WT mice, CALHM1 KO mice had reduced chorda tympani nerve activity elicited by oral application of NaCl, NaLac, and sucrose but normal responses to HCl and NH(4)Cl. Chorda tympani responses to NaCl and NaLac were amiloride sensitive in WT but not KO mice. These results reinforce others demonstrating that multiple transduction pathways make complex, concentration-dependent contributions to salty taste perception. One of these pathways depends on CALHM1 to detect hypertonic NaCl in the mouth and signal the aversive taste of concentrated salt.

Taste dysfunction in BTBR mice due to a mutation of Itpr3, the inositol triphosphate receptor 3 gene.

The BTBR T+ tf/J (BTBR) mouse strain is indifferent to exemplars of sweet, Polycose, umami, bitter, and calcium tastes, which share in common transduction by G protein-coupled receptors (GPCRs). To investigate the genetic basis for this taste dysfunction, we screened 610 BTBR×NZW/LacJ F2 hybrids, identified a potent QTL on chromosome 17, and isolated this in a congenic strain. Mice carrying the BTBR/BTBR haplotype in the 0.8-Mb (21-gene) congenic region were indifferent to sweet, Polycose, umami, bitter, and calcium tastes. To assess the contribution of a likely causative culprit, Itpr3, the inositol triphosphate receptor 3 gene, we produced and tested Itpr3 knockout mice. These were also indifferent to GPCR-mediated taste compounds. Sequencing the BTBR form of Itpr3 revealed a unique 12 bp deletion in Exon 23 (Chr 17: 27238069; Build 37). We conclude that a spontaneous mutation of Itpr3 in a progenitor of the BTBR strain produced a heretofore unrecognized dysfunction of GPCR-mediated taste transduction.

Itpr3 Is responsible for the mouse tufted (tf) locus.

The tf (tufted) locus is responsible for a classic phenotype of hair loss and regrowth in mice. It is a characteristic of the BTBR strain. Here, we use a combination of positional cloning methods and complementation mapping to identify Itpr3, the inositol triphosphate receptor type 3, as the gene responsible for the tf locus.

Obesity in C57BL/6J mice fed diets differing in carbohydrate and fat but not energy content.

To investigate the contributions of carbohydrate and fat to obesity we measured the body weight, body composition and food intake of adult C57BL/6J mice fed ad libitum with various combinations of two semisynthetic diets that differed in carbohydrate and fat but not in protein, micronutrient or energy content. In Experiment 1, involving male mice, body weights were similar in groups fed diets comprised of (by energy) 20% protein, 75% carbohydrate and 5% fat (C75-F5) or 20% protein, 5% carbohydrate and 75% fat (C5-F75). However, mice fed a 50:50 composite mixture of the C75-F5 and C5-F75 diets (i.e., a C40-F40 diet) became substantially more obese. Mice that could choose between the C75-F5 and C5-F75 diets ate equal amounts of each diet and gained almost as much weight as did the group fed C40-F40 diet. Mice switched every day between the C75-F5 and C5-F75 diets gained no more weight than did those fed either diet exclusively. In Experiment 2, male and female mice were fed chow or one of 8 isocaloric diets that differed parametrically in carbohydrate and fat content. Groups fed diets in the middle of the range (i.e., C35-F45 or C45-F35) weighed significantly more and were significantly fatter than were those fed diets with more extreme proportions of carbohydrate and fat (e.g., C75-F5, C5-F75), an effect that was more pronounced in males than females. In Experiment 3 and 4, male mice fed versions of the C40-F40 formulation gained more weight than did those fed the C75-F5 or C5-F75 formulations irrespective of whether the carbohydrate was predominantly sucrose or predominantly starch, or whether the fat was vegetable shortening, corn oil, palm oil or canola oil; the type of carbohydrate or fat had little or no impact on body weight. In all four experiments, energy intakes differed among the diet groups but could not account for the differences in body weight. These results demonstrate that the proportion of carbohydrate and fat in the diet influences body weight independently of energy content, and that the type of carbohydrate or fat has little impact on body weight. Consuming carbohydrate and fat simultaneously or in close temporal proximity exacerbates obesity.

Does eating good-tasting food influence body weight?

Does eating good-tasting food influence body weight? To investigate, we first established some concentrations of sucralose and mineral oil in chow that mice strongly preferred. Then, in Experiment 1, we compared groups of 16 mice fed plain chow (i.e., chow with no additives) to groups fed chow with added (a) sucralose, (b) mineral oil, (c) sucralose and mineral oil, or (d) sucralose on odd days and mineral oil on even days. During a 6-week test, the body weights and body compositions of the five groups never differed. In Experiment 2, we compared groups of 18 mice fed plain chow or plain high-fat diet to groups fed these diets with added sucralose. During a 9-week test, the high-fat diet caused weight gain, but the body weights of mice fed the sucralose-sweetened diets did not differ from those fed the corresponding plain versions. Two-cup choice tests conducted at the end of each experiment showed persisting strong preferences for the diets with added sucralose and/or mineral oil. In concert with earlier work, our results challenge the hypothesis that the orosensory properties of a food influence body weight gain. A good taste can stimulate food intake acutely, and guide selection toward nutrient-dense foods that cause weight gain, but it does not determine how much is eaten chronically.

Macronutrient choice of BTBR.NZW mice congenic for a 21-gene region of chromosome 17.

There has been scant work to investigate the mechanisms influencing macronutrient selection by mice. Here, we measured the consumption and choice of carbohydrate- and fat-containing diets by NZW/LacJ (NZW) and BTBR/T+ tf/J (BTBR) strains. We found that NZW mice voluntarily ate more carbohydrate and less fat than did BTBR mice. Mice with a BTBR background and a heterozygous (BTBR/NZW) congenic region on chromosome 17 between 25.7 and 27.5 Mb (N10 generation) or 26.7 and 27.5 Mb (N12 generation) also ate more carbohydrate and less fat than did homozygous (BTBR/BTBR) littermate controls. Of the 21 known and predicted genes in the congenic interval between 26.7 and 27.5 Mb, we raise for consideration as a causative candidate Itpr3, the inositol triphosphate receptor type 3 gene, which is a component of the GPCR-mediated taste transduction cascade. We speculate that a mutation in Itpr3 influences food choice by impairing the detection of nutrients in the macronutrient-containing diets.