日本理化學研究所的一個研究小組發(fā)現(xiàn)了實驗用小鼠合成荷爾蒙“褪黑激素”的遺傳基因，進而破解了實驗用小鼠雄性性早熟之謎,。研究結果表明,，人工飼養(yǎng)過程中，實驗用小鼠褪黑激素合成酶的遺傳基因發(fā)生了突變,，小鼠不能制造褪黑激素,，導致了雄性小鼠的過早性成熟。這種缺少褪黑激素的小鼠繁衍能力更強,，實驗用小鼠在人類的飼育過程中完成了獨特的進化,。
褪黑激素是大腦松果體在夜間分泌的，與生物鐘和季節(jié)性繁殖調節(jié)有關的一種荷爾蒙,。它是色氨酸在酶的作用下經過連續(xù)合成反應的產物,，最終階段的合成由HIOMT酶主導。研究小組利用理化學研究所保存和收集的小鼠系統(tǒng)樣品和研究資料,，發(fā)現(xiàn)了小鼠合成褪黑激素的酶HIOMT的遺傳基因,。但奇怪的是實驗用小鼠幾乎都不能制造褪黑激素，雖然其遺傳基因測序已經完成,，但卻沒有發(fā)現(xiàn)其體內含有HIOMT的遺傳基因,。基于這個結果,，研究人員從基因組結構和生理學功能兩個方面證實了實驗用小鼠不能制造褪黑激素的理由,，相關論文發(fā)表在3月22日的《美國國家科學院院刊》網絡版上。
自人類開始農耕以來,，小家鼠就生息在人類的生活圈周圍,。有記錄記載飼育研究用小鼠始于100多年前，人們對其進行捕獲并在人工環(huán)境下飼養(yǎng)繁殖小家鼠用于實驗直至今日,。與野生小鼠相比,，人工飼養(yǎng)的實驗用小鼠出現(xiàn)了老實、毛色各樣等各種差別,。除這些簡單外觀的差別之外,，人們還發(fā)現(xiàn)實驗小鼠在癌癥發(fā)病率及荷爾蒙機能等生理學方面的差異。如研究人員在人類以及與小鼠相近的大鼠中發(fā)現(xiàn)了用于合成褪黑激素的HIOMT基因,，但在實驗小鼠中沒有找到,，幾乎所有實驗用小鼠均不能制造褪黑激素。研究發(fā)現(xiàn),，小鼠的HIOMT基因存在于擬常染色體區(qū)域易于引起突變,。由于突變引發(fā)HIOMT酶機能喪失,，導致褪黑激素無法制造，從而造成其性成熟提前,。
在人工環(huán)境下飼養(yǎng)的小鼠性成熟早,，可以快速完成傳宗接代任務，這無論對飼養(yǎng)者還是小鼠本身都有利,。小鼠在飼育設施內喪失褪黑激素的特性,，是一種在特殊環(huán)境下的進化。人工飼育的實驗用小鼠喪失原有特質的現(xiàn)象,，對醫(yī)學,、生物學研究以及多種系統(tǒng)比較研究均具有重要意義。（生物谷Bioon.com）
生物谷推薦原文出處：
PNAS 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.
