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首页> 外文期刊>Molecular and Cellular Biology >A foreign dihydrofolate reductase gene in transgenic mice acts as a dominant mutation.
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A foreign dihydrofolate reductase gene in transgenic mice acts as a dominant mutation.

机译:转基因小鼠中的外源二氢叶酸还原酶基因充当显性突变。

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We have produced 17 lines of transgenic mice by microinjecting a full-length cDNA clone of an altered dihydrofolate reductase (dhfr) gene. The protein specified by this gene carries a point mutation which triples its Km for dihydrofolate and reduces substrate turnover 20-fold relative to the wild-type enzyme. Transgenic mice from different pedigrees, several of which carry a single copy of this gene in different integration sites, manifest an array of similar developmental abnormalities including growth stunting, reduced fertility, pigmentation changes, and skeletal defects. These defects appear in animals heterozygous for the foreign gene. RNA analyses demonstrate significant expression of the cDNA in newborn mice and adult tissues. These findings show that the additional dhfr gene exerts its mutational effects in a dominant fashion, and therefore the data indicate that transgenic mice can serve as models for elucidating mechanisms of dominant mutagenesis.
机译:通过显微注射改变的二氢叶酸还原酶(dhfr)基因的全长cDNA克隆,我们已经生产了17条转基因小鼠品系。由该基因指定的蛋白质带有一个点突变,该突变使二氢叶酸的Km增至三倍,并使底物周转率相对于野生型酶降低20倍。来自不同血统的转基因小鼠,其中一些在不同的整合位点携带该基因的单个拷贝,表现出一系列相似的发育异常,包括生长发育迟缓,生育力降低,色素沉着变化和骨骼缺陷。这些缺陷在外源基因杂合的动物中出现。 RNA分析表明该cDNA在新生小鼠和成年组织中表达明显。这些发现表明,附加的dhfr基因以显性方式发挥其突变作用,因此数据表明转基因小鼠可以作为阐明显性诱变机制的模型。

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