利用生物信息学分析方法对鸡Lpin1基因编码区进行扫描,选取该基因3个引起错义突变的变异位点进行分析,其中c.391G>A位点引起编码氨基酸Asp131→Asn131突变,c.1727C>T位点引起编码氨基酸Ala576→Val576突变,c.2287A>C位点引起...利用生物信息学分析方法对鸡Lpin1基因编码区进行扫描,选取该基因3个引起错义突变的变异位点进行分析,其中c.391G>A位点引起编码氨基酸Asp131→Asn131突变,c.1727C>T位点引起编码氨基酸Ala576→Val576突变,c.2287A>C位点引起编码氨基酸Met763→Leu763突变。应用引入限制性酶切位点PCR(Amplifi-cation-Created Restriction Site PCR,ACRS-PCR)的方法进行引物设计扩增3个突变位点,并通过限制性片段长度多态性(Restriction Fragment Length Polymorphism,RFLP)检测PCR产物,以藏鸡、隐性白羽鸡、藏隐(藏鸡♂×隐性白羽♀)和藏藏隐[藏鸡♂×(藏鸡♂×隐性白羽♀)♀]群体为材料对3个变异位点进行基因型检测,并与胴体性状进行关联分析;同时在5个中国地方鸡种(固始鸡、萧山鸡、北京油鸡、泰和丝羽乌骨鸡和茶花鸡)中进行变异位点的遗传多样性分析。结果表明:(1)鸡Lpin1基因c.1727C>T在不同品种中具丰富的多态性;而另2个位点在所检测的群体中无多态性存在,c.391G>A位点以GG基因型为主,c.2287A>C位点全部为AA基因型;(2)对c.1727C>T位点的遗传多样性分析表明该位点C等位基因占优势地位,且固始鸡和北京油鸡群体基因型分布显著偏离哈代-温伯格平衡定律(P<0.01),在萧山鸡、泰和丝羽乌骨鸡和茶花鸡三品种中基因型分布均符合哈代-温伯格平衡定律。(3)性状关联分析显示c.1727C>T位点与皮下脂肪厚呈显著关联(P<0.05),与腹脂质量呈极显著关联(P<0.01);其中CC基因型个体的皮下脂肪厚显著高于TT基因型个体(P<0.05),极显著高于TC基因型个体(P<0.01)。TT基因型个体的腹脂质量显著高于其他两种基因型个体(P<0.05)。展开更多
N6-methyladenosine(m^(6)A)is one of the most abundant modifications on m RNAs and plays important roles in various biological processes.The formation of m^(6)A is catalyzed by a methyltransferase complex(MTC)containin...N6-methyladenosine(m^(6)A)is one of the most abundant modifications on m RNAs and plays important roles in various biological processes.The formation of m^(6)A is catalyzed by a methyltransferase complex(MTC)containing a key factor methyltransferase-like 3(Mettl3).However,the functions of Mettl3 and m^(6)A modification in hepatic lipid and glucose metabolism remain unclear.Here,we showed that both Mettl3 expression and m^(6)A level increased in the livers of mice with high fat diet(HFD)-induced metabolic disorders.Overexpression of Mettl3 aggravated HFDinduced liver metabolic disorders and insulin resistance.In contrast,hepatocyte-specific knockout of Mettl3 significantly alleviated HFD-induced metabolic disorders by slowing weight gain,reducing lipid accumulation,and improving insulin sensitivity.Mechanistically,Mettl3 depletion-mediated m^(6)A loss caused extended RNA half-lives of metabolism-related genes,which consequently protected mice against HFD-induced metabolic syndrome.Our findings reveal a critical role of Mettl3-mediated m^(6)A in HFD-induced metabolic disorders and hepatogenous diabetes.展开更多
文摘利用生物信息学分析方法对鸡Lpin1基因编码区进行扫描,选取该基因3个引起错义突变的变异位点进行分析,其中c.391G>A位点引起编码氨基酸Asp131→Asn131突变,c.1727C>T位点引起编码氨基酸Ala576→Val576突变,c.2287A>C位点引起编码氨基酸Met763→Leu763突变。应用引入限制性酶切位点PCR(Amplifi-cation-Created Restriction Site PCR,ACRS-PCR)的方法进行引物设计扩增3个突变位点,并通过限制性片段长度多态性(Restriction Fragment Length Polymorphism,RFLP)检测PCR产物,以藏鸡、隐性白羽鸡、藏隐(藏鸡♂×隐性白羽♀)和藏藏隐[藏鸡♂×(藏鸡♂×隐性白羽♀)♀]群体为材料对3个变异位点进行基因型检测,并与胴体性状进行关联分析;同时在5个中国地方鸡种(固始鸡、萧山鸡、北京油鸡、泰和丝羽乌骨鸡和茶花鸡)中进行变异位点的遗传多样性分析。结果表明:(1)鸡Lpin1基因c.1727C>T在不同品种中具丰富的多态性;而另2个位点在所检测的群体中无多态性存在,c.391G>A位点以GG基因型为主,c.2287A>C位点全部为AA基因型;(2)对c.1727C>T位点的遗传多样性分析表明该位点C等位基因占优势地位,且固始鸡和北京油鸡群体基因型分布显著偏离哈代-温伯格平衡定律(P<0.01),在萧山鸡、泰和丝羽乌骨鸡和茶花鸡三品种中基因型分布均符合哈代-温伯格平衡定律。(3)性状关联分析显示c.1727C>T位点与皮下脂肪厚呈显著关联(P<0.05),与腹脂质量呈极显著关联(P<0.01);其中CC基因型个体的皮下脂肪厚显著高于TT基因型个体(P<0.05),极显著高于TC基因型个体(P<0.01)。TT基因型个体的腹脂质量显著高于其他两种基因型个体(P<0.05)。
基金Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA16030000)the National Key R&D Program(Grant Nos.2017YFA0103803,2018YFA0107703,and 2018YFA0801200)+2 种基金the National Natural Science Foundation of China(Grant Nos.31621004 and 31770872)the Key Research Projects of the Frontier Science of the Chinese Academy of Sciences(Grant Nos.QYZDY-SSW-SMC002 and QYZDB-SSW-SMC022)the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.CAS2018133)
文摘N6-methyladenosine(m^(6)A)is one of the most abundant modifications on m RNAs and plays important roles in various biological processes.The formation of m^(6)A is catalyzed by a methyltransferase complex(MTC)containing a key factor methyltransferase-like 3(Mettl3).However,the functions of Mettl3 and m^(6)A modification in hepatic lipid and glucose metabolism remain unclear.Here,we showed that both Mettl3 expression and m^(6)A level increased in the livers of mice with high fat diet(HFD)-induced metabolic disorders.Overexpression of Mettl3 aggravated HFDinduced liver metabolic disorders and insulin resistance.In contrast,hepatocyte-specific knockout of Mettl3 significantly alleviated HFD-induced metabolic disorders by slowing weight gain,reducing lipid accumulation,and improving insulin sensitivity.Mechanistically,Mettl3 depletion-mediated m^(6)A loss caused extended RNA half-lives of metabolism-related genes,which consequently protected mice against HFD-induced metabolic syndrome.Our findings reveal a critical role of Mettl3-mediated m^(6)A in HFD-induced metabolic disorders and hepatogenous diabetes.