Biomedical subjects

Michael G Tordoff

Publications and source records attributed to Michael G Tordoff.

At least 19 recordsLinked to original sources

PubMed2006

Quantitative trait loci for individual adipose depot weights in C57BL/6ByJ x 129P3/J F2 mice.

To understand how genotype influences fat patterning and obesity, we conducted an autosomal genome scan using male and female F(2) hybrids between the C57BL/6ByJ and 129P3/J parental mouse strains. Mice were studied in middle-adulthood and were fed a low-energy, low-fat diet during their lifetime. We measured the weight of the retroperitoneal adipose depot (near the kidney) and the gonadal adipose depot (near the epididymis in males and ovaries in females). An important feature of the analysis was the comparison of linkage results for absolute adipose depot weight and depot weight adjusted for body size, i.e., relative weight. We detected 67 suggestive linkages for six phenotypes, which fell into one of three categories: those specific to absolute but not relative depot weight (Chr 5, 11, and 14), those specific to relative but not absolute depot weight (Chr 9, 15, and 16), and those involving both (Chr 2 and 7). Some quantitative trait loci (QTLs) affected one adipose depot more than another: Retroperitoneal depot weight was linked to Chr 8, 11, 12, and 17, but the linkage effects for the gonadal depot were stronger for Chr 5, 7, and 9. Several linkages were specific to sex; for instance, the absolute weight of gonadal fat was linked to Chromosome 7 in male (LOD = 3.4) but not female mice (LOD = 0.2). Refining obesity as a phenotype may uncover clues about gene function that will assist in positional cloning efforts.

Adipose Tissue↗

PubMed2006

A locus on mouse Chromosome 9 (Adip5) affects the relative weight of the gonadal but not retroperitoneal adipose depot.

To identify the gene or genes on mouse Chromosome 9 that contribute to strain differences in fatness, we conducted an expanded mapping analysis to better define the region where suggestive linkage was found, using the F(2 )generation of an intercross between the C57BL/6ByJ and 129P3/J mouse strains. Six traits were studied: the summed weight of two adipose depots, the weight of each depot, analyzed individually (the gonadal and retroperitoneal depot), and the weight of each depot (summed and individual) relative to body size. We found significant linkage (LOD = 4.6) that accounted for the relative weight of the summed adipose depots, and another for the relative weight of the gonadal (LOD = 5.3) but not retroperitoneal (LOD = 0.9) adipose depot. This linkage is near marker rs30280752 (61.1 Mb, Build 34) and probably is equivalent to the quantitative trait locus (QTL) Adip5. Because the causal gene is unknown, we identified and evaluated several candidates within the confidence interval with functional significance to the body fatness phenotype (Il18, Acat1, Cyp19a1, Crabp1, Man2c1, Neil1, Mpi1, Csk, Lsm16, Adpgk, Bbs4, Hexa, Thsd4, Dpp8, Anxa2, and Lipc). We conclude that the Adip5 locus is specific to the gonadal adipose depot and that a gene or genes near the linkage peak may account for this QTL.

Adipose Tissue↗

PubMed2005

Mice acquire flavor preferences during shipping.

Vigorous motion can cause rodents to develop flavor aversions and show other signs of malaise. We tested whether a flavor aversion could be induced by shipping mice from an animal breeder to a test site. Boxes of 12 male C57BL/6J mice were shipped approximately 950 km from Bar Harbor, ME to Philadelphia, PA by truck. For some boxes, the gel provided for hydration was flavored with almond and for others it was flavored with banana. After the journey, the mice were individually housed and allowed to recover for 5 days. They then received a choice between the two flavors of gel. Contrary to expectations, mice preferred the flavor they had previously ingested during shipping. Controls given flavored gel under similar conditions but while stationary did not show a preference. These results suggest that mice find shipping or its sequelae pleasurable. If mice are travel sick this must be inconsequential relative to other components of the shipping experience.

Animal Feed↗

PubMed2005

No relationship between sequence variation in protein coding regions of the Tas1r3 gene and saccharin preference in rats.

Nearly all mammalian species like sweet-tasting foods and drinks, but there are differences in the degree of 'sweet tooth' both between species and among individuals of the same species. Some individual differences can be explained by genetic variability. Polymorphisms in a sweet taste receptor (Tas1r3) account for a large fraction of the differences in consumption of sweet solutions among inbred mouse strains. We wondered whether mice and rats share the same Tas1r3 alleles, and whether this gene might explain the large difference in saccharin preference among rats. We conducted three experiments to test this. We examined DNA sequence differences in the Tas1r3 gene among rats that differed in their consumption of saccharin in two-bottle choice tests. The animals tested were from an outbred strain (Sprague-Dawley; experiment 1), selectively bred to be high- or low-saccharin consumers (HiS and LoS; experiment 2), or from inbred strains with established differences in saccharin preference (FH/Wjd and ACI; experiment 3). Although there was considerable variation in saccharin preference among the rats there was no variation in the protein-coding regions of the Tas1r3 gene. DNA variants in intronic regions were detected in 1 (of 12) outbred rat with lower-than-average saccharin preference and in the ACI inbred strain, which also has a lower saccharin preference than the FH/Wjd inbred partner strain. Possible effects of these intronic nucleotide variants on Tas1r3 gene expression or the presence of T1R3 protein in taste papillae were evaluated in the ACI and FH/Wjd strains. Based upon the results of these studies, we conclude that polymorphisms in the protein-coding regions of the sweet receptor gene Tas1r3 are uncommon and do not account for individual differences in saccharin preference for these strains of rats. DNA variants in intron 4 and 5 are more common but appear to be innocuous.

Animals↗

PubMed2005

Calcium deprivation increases the palatability of calcium solutions in rats.

Calcium-deprived rats have elevated intakes of CaCl2, other calcium salts, and some non-calcium compounds. We used taste reactivity to examine the effects of calcium deprivation on the palatability of CaCl2 and other solutions. Nine male Sprague-Dawley rats were calcium-deprived by maintenance on a low-calcium diet, and eight replete rats were used as controls. All rats were videotaped during intraoral infusion of the following solutions: 30 and 300 mM CaCl2, 30 mM calcium lactate, 100 and 600 mM NaCl, 30 mM MgCl2, 1 mM quinine.HCl, 2.5 mM sodium saccharin, and deionized water. We counted individual orofacial and somatic movements elicited by the infusions and used them to calculate total ingestive and aversive scores. Relative to controls, calcium-deprived rats gave a significantly larger number of tongue protrusions and had higher total ingestive scores for CaCl2, calcium lactate, NaCl, and MgCl2. Our results suggest that CaCl2, calcium lactate, NaCl, and MgCl2 taste more palatable to rats when they are calcium-deprived than replete, and this may be responsible for the increased intake of these solutions following calcium deprivation.

Analysis of Variance↗

PubMed2005

Influence of the number of repellent-treated and untreated food or water containers on intake by the European starling.

The availability of multiple sources of food and drink has a profound influence on choice behavior in rodents. It is not known how other taxa might respond to the same kind of variation in availability. We tested European starlings (Sturnus vulgaris) with various combinations of unadulterated and repellent-treated (0.025% citronellyl acetate) resources. In Experiment 1, birds drank more plain than repellent-treated water than when given (a) 2 bottles of plain water and 2 of repellent-water, or (b) 3 bottles of plain water and 1 of repellent-water. However, they drank more repellent than water when given 3 bottles of repellent-water and 1 of plain water. Thus, the aversion to the repellent became indifference when repellent-water was abundant. In Experiment 2, birds ate more untreated than treated food when given (a) 1 cup of untreated food and 1 cup of treated food or (b) 2 cups of untreated food and 1 of treated food. They ate equal amounts of untreated and treated food when given 1 cup of untreated food and 2 cups of treated food. These results demonstrate the effect of relative availability on choice, and imply that availability should be considered when using repellents.

Animals↗

PubMed2004

Allelic variation of the Tas1r3 taste receptor gene selectively affects behavioral and neural taste responses to sweeteners in the F2 hybrids between C57BL/6ByJ and 129P3/J mice.

Recent studies have shown that the T1R3 receptor protein encoded by the Tas1r3 gene is involved in transduction of sweet taste. To assess ligand specificity of the T1R3 receptor, we analyzed the association of Tas1r3 allelic variants with taste responses in mice. In the F2 hybrids between the C57BL/6ByJ (B6) and 129P3/J (129) inbred mouse strains, we determined genotypes of markers on chromosome 4, where Tas1r3 resides, measured consumption of taste solutions presented in two-bottle preference tests, and recorded integrated responses of the chorda tympani gustatory nerve to lingual application of taste stimuli. For intakes and preferences, significant linkages to Tas1r3 were found for the sweeteners sucrose, saccharin, and D-phenylalanine but not glycine. For chorda tympani responses, significant linkages to Tas1r3 were found for the sweeteners sucrose, saccharin, D-phenylalanine, D-tryptophan, and SC-45647 but not glycine, L-proline, L-alanine, or L-glutamine. No linkages to distal chromosome 4 were detected for behavioral or neural responses to non-sweet quinine, citric acid, HCl, NaCl, KCl, monosodium glutamate, inosine 5'-monophosphate, or ammonium glutamate. These results demonstrate that allelic variation of the Tas1r3 gene affects gustatory neural and behavioral responses to some, but not all, sweeteners. This study describes the range of ligand sensitivity of the T1R3 receptor using an in vivo approach and, to our knowledge, is the first genetic mapping study of activity in gustatory nerves.

Alleles↗

PubMed2003

No effect of dietary calcium on body weight of lean and obese mice and rats.

Recent epidemiological and animal studies have led to the hypothesis that low dietary calcium intakes contribute to obesity. Here, we evaluated whether calcium influenced the body weight of normal-weight and obese rodents. All experiments involved female C57BL/6J mice or Sprague-Dawley rats fed normal- or high-energy-density diets (3.8 o 4.7 kcal/g). Calcium intake was manipulated by allowing mice to drink sweetened 30 mM CaCl(2) solution or feeding mice and rats diets differing in calcium content (0.2%, 0.6%, o 1.8% Ca(2+)). Blood samples were taken from rats to confirm that the diets had their intended effects on metabolism. There were no effects of the calcium manipulations on energy intake, body weight, or carcass fat content and no simple elation between calciotropic hormones and body weight. One experiment found a significant decrease in body weight gain of lean and obese rats fed the 1.8% Ca(2+) diet, but we suspect that this was due to forced consumption of the unpalatable diet, reducing growth. These studies provide little support for the hypothesis that dietary calcium contributes to the etiology or maintenance of obesity.

Animals↗

PubMed2003

Loci on chromosomes 2, 4, 9, and 16 for body weight, body length, and adiposity identified in a genome scan of an F2 intercross between the 129P3/J and C57BL/6ByJ mouse strains.

Mice have proved to be a powerful model organism for understanding obesity in humans. Single gene mutants and genetically modified mice have been used to identify obesity genes, and the discovery of loci for polygenic forms of obesity in the mouse is an important next step. To pursue this goal, the inbred mouse strains 129P3/J (129) and C57BL/6ByJ (B6), which differ in body weight, body length, and adiposity, were used in an F2 cross to identify loci affecting these phenotypes. Linkages were determined in a two-phase process. In the first phase, 169 randomly selected F2 mice were genotyped for 134 markers that covered all autosomes and the X Chromosome (Chr). Significant linkages were found for body weight and body length on Chr 2. In addition, we detected several suggestive linkages on Chr 2 (adiposity), 9 (body weight, body length, and adiposity), and 16 (adiposity), as well as two suggestive sex-dependent linkages for body length on Chrs 4 and 9. In the second phase, 288 additional F2 mice were genotyped for markers near these regions of linkage. In the combined set of 457 F2 mice, six significant linkages were found: Chr 2 (Bwq5, body weight and Bdln3, body length), Chr 4 (Bdln6, body length, males only), Chr 9 (Bwq6, body weight and Adip5, adiposity), and Chr 16 (Adip9, adiposity), as well as several suggestive linkages (Adip2, adiposity on Chr 2, Bdln4 and Bdln5, body length on Chr 9). In addition, there was a suggestive linkage to body length in males on Chr 9 (Bdln4). For adiposity, there was evidence for epistatic interactions between loci on Chr 9 (Adip5) and 16 (Adip9). These results reinforce the concept that obesity is a complex trait. Genetic loci and their interactions, in conjunction with sex, age, and diet, determine body size and adiposity in mice.

Animals↗

PubMed2003

Lesions of the subfornical organ decrease the calcium appetite of calcium-deprived rats.

There are several indications that neurons in the rat's subfornical organ (SFO) are sensitive to internal calcium status. We investigated the role of the SFO in regulating calcium intake by comparing the consumption of 30 mM CaCl2 by rats with (a) lesions of >90% of the SFO, (b) lesions that left the SFO mostly intact but disconnected its rostroventral stalk, (c) misplaced lesions that spared most of the SFO, or (d) a sham lesion procedure. In one experiment involving calcium-replete rats, these four groups had similar CaCl2 intakes. In another experiment involving calcium-deprived rats, those with lesions of the SFO or its rostroventral stalk consumed less CaCl2 than did those with missed or sham lesions. The SFO therefore appears to play a role in the calcium appetite that accompanies calcium deprivation in rats, most likely through its rostroventral efferents, but it is not important for need-free calcium intake.

Animals↗

PubMed2003

Mouse taste preference tests: why only two bottles?

Two-bottle tests have been used extensively to measure the preference for taste and nutrient solutions but there has been little work with tests involving more than two bottles. Here, we compare the results obtained in two-bottle tests with those obtained in three- and six-bottle tests. In Experiment 1, we measured the preferences for 2 mM saccharin, 50 mM citric acid, 0.3 mM quinine hydrochloride and 75 mM NaCl displayed by 129X1/SvJ (129) and C57BL/6J (B6) mice. Mice drank more taste solution when they received two bottles providing taste solution and one providing water than when they received either a standard two-bottle test or two bottles providing water and one providing taste solution. The three-bottle tests also revealed the left spout side preferences of the 129 strain and were generally better at distinguishing between the 129 and B6 strains (i.e. were more sensitive) than were the two-bottle tests. In Experiment 2, we measured intakes and preferences in tests with six bottles, with one, two, three, four or five containing 75 mM NaCl and the rest containing water. NaCl preferences were monotonically related to the number of NaCl spouts available. A follow-up experiment found similar results whether the index of ingestion was volume intakes or licks. This argues that spillage cannot account for the effect of spout number on taste solution intake. Together, the results suggest that (i) the number of bottles of taste solution and water has a profound influence on taste solution intake and preference, and (ii) three-bottle tests may be more sensitive than two-bottle tests in many circumstances.

Analysis of Variance↗

PubMed2003

Chemosensory factors influencing alcohol perception, preferences, and consumption.

This article presents the proceedings of a symposium at the 2002 RSA/ISBRA Meeting in San Francisco, California, co-organized by Julie A. Mennella and Alexander A. Bachmanov of the Monell Chemical Senses Center. The goal of this symposium was to review the role that chemosensory factors (taste, smell, and chemical irritation) play in the perception, preference, and consumption of alcohol. The presented research focused on both humans and laboratory animals and used a variety of approaches including genetic, developmental, pharmacological, behavioral, and psychophysical studies. The presentations were as follows: (1) Introduction and overview of the chemical senses (Julie A. Mennella and Alexander A. Bachmanov); (2) Taste reactivity as a measure of alcohol palatability and its relation to alcohol consumption in rats (Stephen W. Kiefer); (3) Early learning about the sensory properties of alcohol in laboratory animals (Juan Carlos Molina); (4) Early learning about the sensory properties of alcohol in humans (Julie A. Mennella); (5) Genetic dissection of the ethanol-sweet taste relationship in mice (Alexander A. Bachmanov and Michael Tordoff); and (6) Human genetic variation in taste: connections with alcohol sensation and intake (Valerie B. Duffy and Linda M. Bartoshuk). The symposium concluded with a general discussion.

Alcohol Drinking↗

PubMed2002

Magnesium appetite in the rat.

Rats modify their ingestive behaviour to correct deficiencies of minerals such as sodium and calcium. Here, we examined the effect of magnesium deprivation on the ingestion of MgCl2 and other solutions. Male Sprague-Dawley rats were fed a nutritionally complete or magnesium-deficient diet and were then given 3.2, 10, 32, or 100mM MgCl2, 32mM CaCl2, 32mM NaCl, 10mM HCl, or 2.5mM saccharin, and their intake was measured for 24h in a two-bottle choice test with water. Within the first 5 min, magnesium-deprived subjects given 3.2, 32, or 100mM MgCl2 or 32mM CaCl2 drank significantly more of these solutions than did replete rats. In a separate study, rats fed replete, magnesium-deficient, or calcium-deficient diets were given a three-bottle choice between water, 32mM MgCl2, and 32mM CaCl2. The deprived rats preferred the solution that ameliorated their deficiency; for example, during the first 1h, the magnesium-deprived rats drank 3.1 +/- 0.5ml MgCl2 and 1.1 +/- 0.4ml CaCl2, whereas the calcium-deprived rats drank 1.8 +/- 0.5ml MgCl2 and 3.9 +/- 0.4ml CaCl2. Thus, magnesium deprivation leads to a compensatory appetite for magnesium, and the appetites for magnesium and calcium are distinct and specific. The rapid expression of magnesium appetite suggests that it depends in part on innate, gustatory factors.

Analysis of Variance↗

PubMed2002

Genetic, physical, and comparative map of the subtelomeric region of mouse Chromosome 4.

The subtelomeric region of mouse chromosome (Chr) 4 harbors loci with effects on behavior, development, and disease susceptibility. Regions near the telomeres are more difficult to map and characterize than other areas because of the unique features of subtelomeric DNA. As a result of these problems, the available mapping information for this part of mouse Chr 4 was insufficient to pursue candidate gene evaluation. Therefore, we sought to characterize the area in greater detail by creating a comprehensive genetic, physical, and comparative map. We constructed a genetic map that contained 30 markers and covered 13.3 cM; then we created a 1.2-Mb sequence-ready BAC contig, representing a 5.1-cM area, and sequenced a 246-kb mouse BAC from this contig. The resulting sequence, as well as approximately 40 kb of previously deposited genomic sequence, yielded a total of 284 kb of sequence, which contained over 20 putative genes. These putative genes were confirmed by matching ESTs or cDNA in the public databases to the genomic sequence and/or by direct sequencing of cDNA. Comparative genome sequence analysis demonstrated conserved synteny between the mouse and the human genomes (1p36.3). DNA from two strains of mice (C57BL/6ByJ and 129P3/J) was sequenced to detect single nucleotide polymorphisms (SNPs). The frequency of SNPs in this region was more than threefold higher than the genome-wide average for comparable mouse strains (129/Sv and C57BL/6J). The resulting SNP map, in conjunction with the sequence annotation and with physical and genetic maps, provides a detailed description of this gene-rich region. These data will facilitate genetic and comparative mapping studies and identification of a large number of novel candidate genes for the trait loci mapped to this region.

Animals↗

PubMed2002

Intragastric calcium infusions support flavor preference learning by calcium-deprived rats.

We investigated whether rats can associate the flavor of ingested solutions with the postingestive delivery of calcium. In one series of experiments using the "electronic esophagus" preparation, calcium-deprived rats received pairs of daily one-bottle training trials in which they received intragastric infusions whenever they ingested an arbitrary flavor of Kool Aid. Rats later preferred the flavor associated with infusions of 50 mM CaCl(2) or 50 mM calcium lactate (CaLa), but not with water, 10, 100 or 250 mM CaCl(2) or 100 mM sodium lactate (NaLa). In another experiment, rats had simultaneous access to two arbitrary flavors, ingestion of one of which produced intragastric infusion of 50 mM CaCl(2), 75 mM NaCl or water. Only the rats given 50 mM CaCl(2) developed a preference for the flavor associated with the infusion. The preference for calcium infusions was not as large as that seen for orally ingested calcium. Nevertheless, these results show that 50 mM calcium infusions are rewarding to calcium-deprived rats. They thus suggest that rats can associate flavor ingestion with the postingestive benefits of consuming calcium.

Analysis of Variance↗

PubMed2002

Some failures of intragastric NaCl infusions to support flavor preference learning.

Rats can acquire conditioned flavor preferences based on the postingestive delivery of energy-rich nutrients. Here, we tried to condition flavor preferences to the postingestive delivery of the nutrient, sodium. Three experiments were conducted. In one, sodium-depleted rats were allowed to choose between two arbitrary flavors for 8 days. Ingestion of one of the flavors initiated infusions of one of two volumes of 150 mM NaCl, whereas ingestion of the other flavor had no effect. The rats showed no preference for the flavor paired with NaCl infusion. In another, sodium-depleted rats were given two pairs of 24-h one-bottle training trials. Ingestion of the flavor presented during one trial initiated infusions of water or one of four concentrations of NaCl (75, 150, 300 or 450 mM NaCl). Ingestion of the flavor presented on the other trial in each pair had no effect. In a subsequent two-bottle choice between the two flavors, the rats were either indifferent to (water, 75 and 150 mM) or avoided (300 or 450 mM) the infusion-paired flavor. In the third study, replete rats were trained as in the previous experiment with 150 mM NaCl as the infusate and tested after sodium deficiency was induced by furosemide. These animals avoided the flavor paired with NaCl infusion. We conclude that rats cannot associate an arbitrary taste with the beneficial effects of postingestive delivery of NaCl, or if they can, this occurs only under rare circumstances.

Animals↗

PubMed2002

Voluntary consumption of NaCl, KCl, CaCl2, and NH4Cl solutions by 28 mouse strains.

Male mice from 28 inbred strains (129P3/J, A/J, AKR/J, BALB/cByJ, BUB/BnJ, C3H/HeJ, C57BL/6J, C57L/J, CAST/Ei, CBA/J, CE/J, DBA/2J, FVB/NJ, I/LnJ, KK/H1J, LP/J, NOD/LtJ, NZB/B1NJ, P/J, PL/J, RBF/DnJ, RF/J, RIIIS/J, SEA/GnJ, SJL/J, SM/J, SPRET/Ei, and SWR/J) were tested with NaCl (75-450 mM), KCl (30-300 mM), CaCl2 (3-100 mM), and NH4Cl (10-300 mM) solutions using two-bottle preference tests with water as the second choice. For each mineral, there was a wide range of strain variation in solution intakes and preferences. This variation had a substantial genetic component as assessed using heritability estimates. In most cases, the strain means were continuously distributed; however, strains with deviating high or low intakes or preferences were also observed. The associations among the responses to different minerals were only modest, suggesting distinct genetic controls of sodium, potassium, calcium, and ammonium consumption. These results provide a valuable resource for investigators who wish to identify genes involved in the regulation of mineral consumption and balance.

Ammonium Chloride↗

PubMed2002

Food intake, water intake, and drinking spout side preference of 28 mouse strains.

Male mice from 28 inbred strains (129P3/J, A/J, AKR/J, BALB/cByJ, BUB/BnJ, C3H/HeJ, C57BL/6J, C57L/J, CAST/Ei, CBA/J, CE/J, DBA/2J, FVB/NJ, I/LnJ, KK/H1J, LP/J, NOD/LtJ, NZB/B1NJ, P/J, PL/J, RBF/DnJ, RF/J, RIIIS/J, SEA/GnJ, SJL/J, SM/J, SPRET/Ei, and SWR/J) were fed chow and had access to two water bottles. Body weight, food intake, water intake, and drinking spout side preference were measured. There were large strain differences in all the measures collected, with at least a two-fold difference between strains with the lowest and the highest trait values. Estimates of heritability ranged from 0.36 (spout side preference) to 0.87 (body weight). Body weight, food intake, and water intake were interrelated among the strains, although substantial strain variation in food and water intakes independent from body weight was present. The strain differences described here provide useful information for designing mutagenesis screens and choosing strains for genetic mapping studies.

Animals↗