Molecular genetic basis of rapid and slow acetylation in mice.
Molecular genetic basis of rapid and slow acetylation in mice.
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DOI：
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发表时间：
1991-08
影响因子：
3.6
通讯作者：
K. Martell;K. P. Vatsis;W. Weber
中科院分区：
文献类型：
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作者：
K. Martell;K. P. Vatsis;W. Weber
在人类乙酰化多态性的近交系小鼠模型中研究了N-乙酰化多态性的分子遗传学基础。从C57 BL/6 J（B6）小鼠（快速乙酰化）基因组文库中分离出两个基因组克隆，Nat 1和Nat 2。Nat 1和Nat 2基因都具有870个核苷酸的无内含子编码区，并且与人、兔和鸡的N-乙酰基转移酶具有大于47%的推导氨基酸相似性。通过聚合酶链反应从A/J（A）小鼠（慢乙酰化）基因组DNA中扩增Nat 1和Nat 2，随后测序显示，Nat 1在B6和A小鼠中是相同的，而Nat 2包含一个核苷酸变化，从B6的腺嘌呤到A小鼠的胸腺嘧啶。这种核苷酸取代将B6中99位的推测氨基酸从天冬酰胺改变为A小鼠中的异亮氨酸。亲水性分析表明，这种氨基酸的变化改变了亲水性的侧翼肽段在NAT 2从亲水性的B6小鼠到疏水性的A小鼠。氨基酸的变化发生在基因的一个区域，在人类或兔NAT 2中尚未报道多态性，可能代表N-乙酰转移酶活性的重要结构域。Nat 1和Nat 2在B6小鼠中具有相同的5'到3'方向;这两个基因被大约9个内切酶分开，Nat 1位于Nat 2的5'。
The molecular genetic basis of N-acetylation polymorphism has been investigated in inbred mouse models of the human acetylation polymorphism. Two genomic clones, Nat1 and Nat2, were isolated from a C57BL/6J (B6) mouse (rapid acetylator) genomic library. The Nat1 and Nat2 genes both have intronless coding regions of 870 nucleotides and display greater than 47% deduced amino acid similarity with human, rabbit, and chicken N-acetyltransferases. Amplification of Nat1 and Nat2 from A/J (A) mouse (slow acetylator) genomic DNA by the polymerase chain reaction and subsequent sequencing revealed that Nat1 was identical in B6 and A mice, whereas Nat2 contained a single nucleotide change from adenine in B6 to thymine in A mice. This nucleotide substitution changes the deduced amino acid at position 99 from asparagine in B6 to isoleucine in A mice. Hydropathy analysis revealed that this amino acid change alters the hydropathy of the flanking peptide segment in NAT2 from hydrophilic in the B6 mouse to hydrophobic in the A mouse. The amino acid change occurs in a region of the gene where no polymorphism has yet been reported in human or rabbit NAT2 and may represent an important structural domain for N-acetyltransferase activity. Nat1 and Nat2 have the same 5' to 3' orientation in the B6 mouse; the two genes are separated by approximately 9 kilobases, with Nat1 located 5' of Nat2.