一項研究發(fā)現(xiàn),，阻斷調(diào)控著甜味和鮮味感受的兩種蛋白的功能會導致雄性小鼠不育。人們發(fā)現(xiàn)TAS1R族味覺受體的成員及其被稱為味蛋白的相關(guān)蛋白在味蕾的糖和氨基酸感受方面起作用,，從那以后人們發(fā)現(xiàn)了它們在其他組織中表達,，盡管它們在口腔之外的功能尚不明確。Bedrich Mosinger及其同事發(fā)現(xiàn),，味蛋白的α-亞單位——味覺受體TAS1R3 和 GNAT3在小鼠的睪丸和精子中表達,。為了調(diào)查這些蛋白的功能，這組作者嘗試刪除了小鼠的這些基因的兩份拷貝,，但是只得到了2只雄性雙零后代——盡管在9個月期間有許多交配嘗試,。這兩只雄性小鼠都有不能游動的精子，但是其他方面看上去正常,。為了進一步獲得TAS1R3 和 GNAT3在雄性生殖力方面的作用的見解,，這組作者開發(fā)了一種雙零小鼠模型，它表達了一種人類版本的TAS1R3受體,。對這種小鼠使用人類TAS1R3的化學抑制劑時導致了雄性的臨時不育,，原因是精子畸形和無功能。這組作者說，這些發(fā)現(xiàn)提示“味覺”基因TAS1R3 和 GNAT3可能對于精子發(fā)育和成熟具有重要作用,。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
