日本理化学研究所的一个研究小组发现了实验用小鼠合成荷尔蒙“褪黑激素”的遗传基因，进而破解了实验用小鼠雄性性早熟之谜。
褪黑激素是大脑松果体在夜间分泌的，与生物钟和季节性繁殖调节有关的一种荷尔蒙。它是色氨酸在酶的作用下经过连续合成反应的产物，最终阶段的合成由HIOMT酶主导。
研究结果表明，人工饲养过程中，实验用小鼠褪黑激素合成酶的遗传基因发生了突变，小鼠不能制造褪黑激素，导致了雄性小鼠的过早性成熟。这种缺少褪黑激素的小鼠繁衍能力更强，实验用小鼠在人类的饲育过程中完成了独特的进化。
研究小组利用理化学研究所保存和收集的小鼠系统样品和研究资料，发现了小鼠合成褪黑激素的酶HIOMT的遗传基因。但奇怪的是实验用小鼠几乎都不能制造褪黑激素，虽然其遗传基因测序已经完成，但却没有发现其体内含有HIOMT的遗传基因。基于这个结果，研究人员从基因组结构和生理学功能两个方面证实了实验用小鼠不能制造褪黑激素的理由，相关论文发表在3月22日的PNAS网络版上。
自人类开始农耕以来，小家鼠就生息在人类的生活圈周围。有记录记载饲育研究用小鼠始于100多年前，人们对其进行捕获并在人工环境下饲养繁殖小家鼠用于实验直至今日。与野生小鼠相比，人工饲养的实验用小鼠出现了老实、毛色各样等各种差别。除这些简单外观的差别之外，人们还发现实验小鼠在癌症发病率及荷尔蒙机能等生理学方面的差异。如研究人员在人类以及与小鼠相近的大鼠中发现了用于合成褪黑激素的HIOMT基因，但在实验小鼠中没有找到，几乎所有实验用小鼠均不能制造褪黑激素。研究发现，小鼠的HIOMT基因存在于拟常染色体区域易于引起突变。由于突变引发HIOMT酶机能丧失，导致褪黑激素无法制造，从而造成其性成熟提前。
在人工环境下饲养的小鼠性成熟早，可以快速完成传宗接代任务，这无论对饲养者还是小鼠本身都有利。小鼠在饲育设施内丧失褪黑激素的特性，是一种在特殊环境下的进化。人工饲育的实验用小鼠丧失原有特质的现象，对医学、生物学研究以及多种系统比较研究均具有重要意义。
生物谷推荐原文出处：
PNAS March 22, 2010, doi: 10.1073/pnas.0914399107
Genetic variation of melatonin productivity in laboratory mice under domestication
Takaoki Kasaharaa,1, Kuniya Abeb, Kazuyuki Mekadac, Atsushi Yoshikic, and Tadafumi Katoa,1
Melatonin is a pineal hormone produced at night; however, many strains of laboratory mice are deficient in melatonin. Strangely enough, the gene encoding HIOMT enzyme (also known as ASMT) that catalyzes the last step of melatonin synthesis is still unidentified in the house mouse (Mus musculus) despite the completion of the genome sequence. Here we report the identification of the mouse Hiomt gene, which was mapped to the pseudoautosomal region (PAR) of sex chromosomes. The gene was highly polymorphic, and nonsynonymous SNPs were found in melatonin-deficient strains. In C57BL/6 strain, there are two mutations, both of which markedly reduce protein expression. Mutability of the Hiomt likely due to a high recombination rate in the PAR could be the genomic basis for the high prevalence of melatonin deficiency. To understand the physiologic basis, we examined a wild-derived strain, MSM/Ms, which produced melatonin more under a short-day condition than a long-day condition, accompanied by increased Hiomt expression. We generated F2 intercrosses between MSM/Ms and C57BL/6 strains and N2 backcrosses to investigate the role of melatonin productivity on the physiology of mice. Although there was no apparent effect of melatonin productivity on the circadian behaviors, testis development was significantly promoted in melatonin-deficient mice. Exogenous melatonin also had the antigonadal action in mice of a melatonin-deficient strain. These findings suggest a favorable impact of melatonin deficiency due to Hiomt mutations on domestic mice in breeding colonies.
