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N-acetyltransferase 2 activity and folate levels.

机译：N-乙酰基转移酶2的活性和叶酸水平。

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AIMS: To determine whether increased N-acetyltransferase (NAT) activity might have a toxic effect during development and an influence on folate levels since previous work has shown that only low levels of exogenous NAT can be achieved in constitutionally transgenic mice (Cao et al. 2005). MAIN METHODS: A human NAT1 tet-inducible construct was used that would not be expressed until the inducer was delivered. Human NAT1 cDNA was cloned into pTRE2 and injected into mouse oocytes. Two transgenic lines were crossed to mouse line TgN(rtTahCMV)4Uh containing the CMV promoted "tet(on)". Measurements of red blood cell folate levels in inbred strains of mice were performed. KEY FINDINGS: Only low levels of human NAT1 could be achieved in kidney (highly responsive in other studies) whether the inducer, doxycycline, was given by gavage or in drinking water. An inverse correlation of folate levels with Nat2 enzyme activity was found. SIGNIFICANCE: Since increasing NAT1 activity decreases folate in at least one tissue, the detrimental effect of expression of human NAT1 in combination with endogenous mouse Nat2 may be a consequence of increased catabolism of folate.
机译：目的：为了确定增加的N-乙酰基转移酶（NAT）活性在发育过程中是否可能具有毒性作用以及对叶酸水平的影响，因为先前的研究表明，在体质转基因小鼠中只能实现低水平的外源NAT（Cao等。 2005年）。主要方法：使用人NAT1 tet诱导型构建体，直到诱导剂被递送才表达。将人NAT1 cDNA克隆到pTRE2中，并注入小鼠卵母细胞中。将两个转基因品系与含有CMV促进的“ tet（on）”的小鼠品系TgN（rtTahCMV）4Uh杂交。进行了小鼠近交系中红细胞叶酸水平的测量。关键发现：无论是通过强饲法还是在饮用水中给予强力霉素诱导剂，在肾脏中仅能获得低水平的人NAT1（在其他研究中反应强烈）。发现叶酸水平与Nat2酶活性呈负相关。意义：由于增加的NAT1活性降低了至少一种组织中的叶酸，因此人NAT1与内源性小鼠Nat2结合表达的有害作用可能是叶酸分解代谢增加的结果。

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