POMT2基因在哺乳动物寒冷适应中的分子生物学机制

在动物界，存在一种特殊的生物学现象，冬眠，它是某些动物在冬季外界环境条件恶劣时，例如食物和水的匮乏、天气寒冷等，而产生的一种适应机制。本研究基于申请人前期以冬眠哺乳动物作为研究对象，通过生物信息学手段对多个具有冬眠特性的哺乳动物基因组序列进行比较分析，发现POMT2基因在多个冬眠动物及大多生活在寒冷区域的哺乳动物中存在R->Q突变,推测该基因与寒冷适应相关。结合前人在黑腹果蝇中的研究，发现果蝇中的一种嗜冷突变体，正是由于POMT2基因作用的目的蛋白Dystroglycan表达的降低诱导了果蝇的耐寒性，从而偏向选择较低的生存温度，这也暗示了该基因在温度适应方面存在重要的功能。本项目拟通过结合分子层面的酶活性分析和蛋白表达、细胞层面的活性分析以及动物模型构建POMT2基因点突变小鼠观察动物行为和生理表型，从多个角度探索该基因在哺乳动物甚至冬眠动物中寒冷适应的生物学机制。

In the animal kingdom, there is a special biological phenomenon, hibernation, it is an adaptation mechanism in winter when the external environment conditions are harsh, such as the lack of food and water, low temperature. This study is based on the previous research based on comparative genome analysis of hibernating mammals through bioinformatics methods. We found POMT2 gene in multiple hibernating animals and a great many mammals live in the cold area contain a R -> Q mutation, indicating the genes related to cold adaptation. In combination with previous studies in Drosophila melanogaster, a kind of psychrophilic mutant reduced expression of the target protein of POMT2,Dystroglycan, induced the cold tolerance of Drosophila melanogaster, and thus preferred to live at a lower temperature, which also suggested this gene has an important function in temperature adaptation. This study intends to combine enzyme activity analysis, protein expression at the molecular level, activity analysis at the cell level and animal model construction of POMT2 point mutation mouse to observe animal behavior and physiological phenotype, so as to explore the cold adaptation biological mechanism of POMT2 in mammals and even hibernating animals from multiple perspectives.