TARGETING AND GERM-LINE TRANSMISSION OF A NULL MUTATION AT THE METALLOTHIONEIN I-LOCI AND II-LOCI IN MOUSE
TARGETING AND GERM-LINE TRANSMISSION OF A NULL MUTATION AT THE METALLOTHIONEIN I-LOCI AND II-LOCI IN MOUSE
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DOI：
10.1073/pnas.90.17.8088
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发表时间：
1993-09-01
影响因子：
11.1
通讯作者：
CHOO, KHA
中科院分区：
文献类型：
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作者：
MICHALSKA, AE;CHOO, KHA
我们报道了金属硫蛋白MT-I和MT-II基因缺陷转基因小鼠的产生。通过同源重组将突变引入胚胎干细胞。由靶向胚胎干细胞产生的嵌合鼠通过它们的生殖系传递被破坏的等位基因。纯合子动物是活着出生的，表现出正常和可生育的表型。通过直接测定肝脏提取液中的MT蛋白，证实了MT蛋白的缺失。用中等水平的CdSO4攻击突变动物表明它们比野生动物对镉毒性更敏感。这些小鼠应该提供一个有用的模型，以便详细研究MT-I和MT-II的生理作用。
We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4 indicated their greater susceptibility to cadmium toxicity than wild-type animals. These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II.