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Spermatogenesis and Testis Development Are Normal in Mice Lacking Testicular Orphan Nuclear Receptor 2

机译:精子发生和睾丸发育正常的小鼠缺乏睾丸孤儿核受体2。

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Early in vitro cell culture studies suggested that testicular orphan nuclear receptor 2 (TR2), a member of the nuclear receptor superfamily, may play important roles in the control of several pathways including retinoic acids, vitamin D, thyroid hormones, and ciliary neurotrophic factor. Here we report the surprising results showing that mice lacking TR2 are viable and have no serious developmental defects. Male mice lacking TR2 have functional testes, including normal sperm number and motility, and both male and female mice lacking TR2 are fertile. In heterozygous TR2+/? male mice we found that β-galactosidase, the indicator of TR2 protein expression, was first detected at the age of 3 weeks and its expression pattern was restricted mainly in the spermatocytes and round spermatids. These protein expression patterns were further confirmed with Northern blot analysis of TR2 mRNA expression. Together, results from TR2-knockout mice suggest that TR2 may not play essential roles in spermatogenesis and normal testis development, function, and maintenance. Alternatively, the roles of TR2 may be redundant and could be played by other close members of the nuclear receptor superfamily such as testicular orphan receptor 4 (TR4) or unidentified orphan receptors that share many similar functions with TR2. Further studies with double knockouts of both orphan nuclear receptors, TR2 and TR4, may reveal their real physiological roles.
机译:早期的体外细胞培养研究表明,睾丸孤儿核受体2(TR2)是核受体超家族的成员,可能在控制多种途径(包括视黄酸,维生素D,甲状腺激素和睫状神经营养因子)中发挥重要作用。在这里我们报告令人惊讶的结果,表明缺乏TR2的小鼠是可行的,没有严重的发育缺陷。缺乏TR2的雄性小鼠具有正常的睾丸功能,包括正常的精子数量和运动能力,而缺乏TR2的雄性和雌性小鼠均具有生育能力。在杂合的TR2 + /?雄性小鼠中,我们发现在3周龄时首次检测到TR2蛋白表达的指标β-半乳糖苷酶,并且其表达模式主要局限于精母细胞和圆形细胞。精子。通过TR2 mRNA表达的Northern印迹分析进一步证实了这些蛋白质表达模式。在一起,从TR2基因敲除小鼠的结果表明,TR2可能不会在精子发生和正常睾丸的发育,功能和维持中发挥重要作用。或者,TR2的作用可能是多余的,并且可以由核受体超家族的其他近亲成员扮演,例如睾丸孤儿受体4(TR4)或与TR2具有许多相似功能的未确定的孤儿受体。对两个孤儿核受体TR2和TR4进行双重敲除的进一步研究可能揭示了它们的真正生理作用。

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