The role of the Sac locus in the alcohol taste preference in inbred mouse strains.
The role of the Sac locus in the alcohol taste preference in inbred mouse strains.
复制标题
囊基因座在近交系小鼠品系的酒精味觉偏好中的作用。
DOI：
10.1134/s001249661003004x
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Bachmanov,AA
中科院分区：
文献类型：
--
作者：
Murovets,VO;Zolotarev,VA;Bachmanov,AA
Genetic differences in chemosensory perception of alcohol (taste, smell, and chemical irritation) influence significantly the alcohol preference in both animals and humans [1]. To find out the phenotypic markers of alcohol addiction, of special interest is the positive association between the preference of sweet solutions and an increased alcohol intake, which are characteristic of both rodents [2–4] and humans [5]. The genetic nature of sweet preference has been first proved in [6], where the Sac locus responsible for a high saccharin consumption was identified in mice. The gene Tas1r3 [7] localized to the fourth mouse and first human chromosomes was later established to correspond to the Sac locus and encode T1R3 protein in receptor cells of mammalian taste epithelium [8]. The heterodimeric protein complex T1R2/T1R3 [7, 9, 10] plays the major role in the sweet taste perception [11]. Inbred mouse strains carrying the Sacb taster allele, eg the C57BL/6J strain [6, 7], which prefer sweet solutions and ethanol to water, are assumed to be prone to alcohol consumption because of reacting to the sweet component of its taste [3]. Indeed, the strains with less sensitive (non-taster) allele (Sacd for strain 129P3/J)[12] and especially Tas1r3 knockouts [7, 9, 13], which were derived from the strains with the taster allele Sac, exhibited much less preference for sugar and alcohol solutions in long-term preference tests. However, these testing techniques, although most commonly used, do not permit differentiating the role of taste from the postabsorptive effects (intoxicating and metabolic) in the reaction of alcohol preference. Further study is also required to confirm the perception of the ethanol sweet component by mice, as well as the fact that T1R3 protein is responsible for the perception. In this study, we used the brief-access taste test minimizing the time of contact with the test substance and reducing the volume of its consumption. As a result, the contribution of postabsorptive effects is reduced. Here, we analyzed the response of C57BL/6ByJ, 129P3/J, and Tas1r3-knockout mice to alcohol and two prototypical taste components, sweet and bitter. The presence of the non-taster allele of the Sacd locus in 129P3/J mice or complete absence of the Sac locus (Tas1r3−/− mice) was found to predetermine rejection of ethanol. Note that Sac affected neither perception of the bitter component nor the gustatory detection of ethanol.This study, approved by the Bioethics Committee of Pavlov Institute of Physiology, was performed on four-to six-month-old mice weighing 20–30 g (both males and females). Two inbred strains, 129P3/J (129; n= 31) and C57BL/6ByJ (B6; n= 37) were purchased from the Jackson Laboratory, Bar Harbor, United States. The gene-knockout Tas1r3−/− mice (n= 14) derived from C57BL/6ByJ [13] were kindly provided by Dr. RF Margolskee (Mount Sinai School of Medicine, NY, United States). During the brief-access test, controlled presentation and measurement of the consumption of small volumes of taste substances were performed using a Davis MS-160 licometer (DiLog Instruments, Tallahassee, FL, United States), which recorded the number of tongue licking movements and the inter-lick intervals (ILI), as well as the latency to start licking. Before testing, the animals did not receive water for 22–23 h (total water deprivation for testing ethanol and quinine and partial deprivation
