This is a project to discover the genetic controls that are responsible for the consumption of calcium, magnesium, potassium and sodium. We have already identified several quantitative trait loci (QTLs) related to consumption of these minerals. We propose here to identify the genes underlying some of these QTLs. To do this, we will first produce congenic strains of mice with introgressed QTL- containing chromosomal fragments. This will be done using either a classic selection-by-genotype approach or by taking advantage of recently developed consomic strains. As an example of the classic approach, we propose to complete production of congenic mouse lines that isolate a QTL on Chr 17 that has impressively high LOD scores for CaCl2 preference (LOD = 45) and saccharin preference (LOD = 100). As an example of the consomic-origin approach, we propose to produce congenic lines to isolate a QTL on Chr 5, with a LOD score for NaCl preference of 8.5. To our knowledge, this will be the first QTL for sodium consumption to be characterized. Once congenic strains are established, we will evaluate candidate genes residing in the congenic interval. This will be done using a combination of in silico analyses, gene expression profiling, and related methods. If necessary, licking responses and gustatory electrophysiology will be recorded to determine the site of gene action. The goal will be to reduce the list of candidate genes to a number that can be assessed using genetically engineered mice. Finding genes responsible for the consumption of minerals will help us understand why people do not consume satisfactory amounts of them. Low intakes of calcium, magnesium and potassium, and high intakes of sodium, have been linked to the etiology of many diseases affecting the U.S. population, including hypertension, obesity, osteoporosis, and some forms of cancer. The results of the studies proposed here will expose the mechanisms underlying mineral consumption. With this knowledge, it will be possible to target new treatments and strategies that rectify the inadequate intakes and thus ameliorate or eliminate the diseases.

Public Health Relevance

This is a proposal to discover the genetic controls of mineral consumption. Low intakes of calcium, magnesium and potassium, and high intakes of sodium, have been linked to the etiology of many diseases affecting the U.S. population, including hypertension, obesity, osteoporosis, and some forms of cancer. To understand why people do not consume satisfactory amounts of minerals it is fundamental to find the underlying genes responsible for mineral consumption. The information provided by this project will illuminate the basic mechanisms underlying why we choose to consume particular foods and drinks containing minerals. This is important for guiding nutritional interventions and policy. It will also be possible to target new treatments and strategies that rectify the inadequate intakes and thus ameliorate or eliminate the diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
3R01DC010393-04S1
Application #
8672784
Study Section
Molecular Neurogenetics Study Section (MNG)
Program Officer
Sullivan, Susan L
Project Start
2009-09-30
Project End
2013-07-31
Budget Start
2013-06-15
Budget End
2013-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$6,395
Indirect Cost
$2,068
Name
Monell Chemical Senses Center
Department
Type
DUNS #
088812565
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Tordoff, Michael G; Ellis, Hillary T; Aleman, Tiffany R et al. (2014) Salty taste deficits in CALHM1 knockout mice. Chem Senses 39:515-28
Tordoff, Michael G; Downing, Arnelle; Voznesenskaya, Anna (2014) Macronutrient selection by seven inbred mouse strains and three taste-related knockout strains. Physiol Behav 135:49-54
Taruno, Akiyuki; Vingtdeux, Valerie; Ohmoto, Makoto et al. (2013) CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 495:223-6
Tordoff, Michael G; Jaji, Samira A; Marks, Jacob M et al. (2012) Macronutrient choice of BTBR.NZW mice congenic for a 21-gene region of chromosome 17. Physiol Behav 106:556-61