Positional cloning of the mouse saccharin preference (Sac) locus
Positional cloning of the mouse saccharin preference (Sac) locus
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DOI：
10.1093/chemse/26.7.925
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发表时间：
2001-09-01
期刊：
影响因子：
3.5
通讯作者：
Beauchamp, GK
中科院分区：
文献类型：
--
作者：
Bachmanov, AA;Li, X;Beauchamp, GK
甜味剂摄入量的近交系小鼠之间的差异部分地由糖精偏好（Sac）基因座的等位基因变异决定。遗传和物理作图限制了一个关键的基因组间隔，包含囊到一个194 kb的DNA片段。该区域的测序和注释鉴定了编码推定味觉受体T1 R家族的第三个成员T1 R3的基因（Tas 1 r3）。通过连续回交的194 kb的染色体片段含有Tas 1 r3等位基因从高甜味剂偏好的C57 BL/6 ByJ菌株到低甜味剂偏好的129 P3/J菌株的遗传背景上的渐渗拯救了其低甜味剂偏好表型。Tas 1 r3的多态性可能具有功能意义，通过分析基因组序列和亲缘关系较远的小鼠品系的甜味剂-p参考表型来鉴定。tas 1 r3有两个常见的单倍型，由六个单核苷酸多态性组成：一个单倍型在甜味剂偏好升高的小鼠品系中发现，另一个在对甜味剂相对不敏感的品系中发现。这项研究提供了令人信服的证据，表明Tas 1 r3相当于Sac基因座，T1 R3受体对甜味剂有反应。
Differences in sweetener intake among inbred strains of mice are partially determined by allelic variation of the saccharin preference (Sac) locus. Genetic and physical mapping limited a critical genomic interval containing Sac to a 194 kb DNA fragment. Sequencing and annotation of this region identified a gene (Tas1r3) encoding the third member of the T1R family of putative taste receptors, T1R3. Introgression by serial backcrossing of the 194 kb chromosomal fragment containing the Tas1r3 allele from the high-sweetener-preferring C57BL/6ByJ strain onto the genetic background of the low-sweetener-preferring 129P3/J strain rescued its low-sweetener-preference phenotype. Polymorphisms of Tas1r3 that are likely to have functional significance were identified using analysis of genomic sequences and sweetener-p reference phenotypes of genealogically distant mouse strains. Tas1r3 has two common haplotypes, consisting of six single nucleotide polymorphisms: one haplotype was found in mouse strains with elevated sweetener preference and the other in strains relatively indifferent to sweeteners. This study provides compelling evidence that Tas1r3 is equivalent to the Sac locus and that the T1R3 receptor responds to sweeteners.