一项研究发现，阻断调控着甜味和鲜味感受的两种蛋白的功能会导致雄性小鼠不育。人们发现TAS1R族味觉受体的成员及其被称为味蛋白的相关蛋白在味蕾的糖和氨基酸感受方面起作用，从那以后人们发现了它们在其他组织中表达，尽管它们在口腔之外的功能尚不明确。Bedrich Mosinger及其同事发现，味蛋白的α-亚单位——味觉受体TAS1R3 和 GNAT3在小鼠的睾丸和精子中表达。为了调查这些蛋白的功能，这组作者尝试删除了小鼠的这些基因的两份拷贝，但是只得到了2只雄性双零后代——尽管在9个月期间有许多交配尝试。这两只雄性小鼠都有不能游动的精子，但是其他方面看上去正常。为了进一步获得TAS1R3 和 GNAT3在雄性生殖力方面的作用的见解，这组作者开发了一种双零小鼠模型，它表达了一种人类版本的TAS1R3受体。对这种小鼠使用人类TAS1R3的化学抑制剂时导致了雄性的临时不育，原因是精子畸形和无功能。这组作者说，这些发现提示“味觉”基因TAS1R3 和 GNAT3可能对于精子发育和成熟具有重要作用。（生物谷Bioon.com）
生物谷推荐英文摘要：
Pnas 10.1073/pnas.1302827110
Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility
Bedrich Mosingera,1, Kevin M. Reddinga, M. Rockwell Parkera, Valeriya Yevshayevab, Karen K. Yeea, Katerina Dyominaa, Yan Lia, and Robert F. Margolskeea
TAS1R taste receptors and their associated heterotrimeric G protein gustducin are involved in sugar and amino acid sensing in taste cells and in the gastrointestinal tract. They are also strongly expressed in testis and sperm, but their functions in these tissues were previously unknown. Using mouse models, we show that the genetic absence of both TAS1R3, a component of sweet and amino acid taste receptors, and the gustducin α-subunit GNAT3 leads to male-specific sterility. To gain further insight into this effect, we generated a mouse model that expressed a humanized form of TAS1R3 susceptible to inhibition by the antilipid medication clofibrate. Sperm formation in animals without functional TAS1R3 and GNAT3 is compromised, with malformed and immotile sperm. Furthermore, clofibrate inhibition of humanized TAS1R3 in the genetic background of Tas1r3-/- Gnat3-/- doubly null mice led to inducible male sterility. These results indicate a crucial role for these extraoral “taste” molecules in sperm development and maturation. We previously reported that blocking of human TAS1R3, but not mouse TAS1R3, can be achieved by common medications or chemicals in the environment. We hypothesize that even low levels of these compounds can lower sperm count and negatively affect human male fertility, which common mouse toxicology assays would not reveal. Conversely, we speculate that TAS1R3 and GNAT3 activators may help infertile men, particularly those that are affected by some of the mentioned inhibitors and/or are diagnosed with idiopathic infertility involving signaling pathway of these receptors.
