Prenatal lethality in a transgenic mouse line is the result of a chromosomal translocation.
Prenatal lethality in a transgenic mouse line is the result of a chromosomal translocation.
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转基因小鼠系的产前致死率是染色体易位的结果。
DOI：
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发表时间：
1988
影响因子：
11.1
通讯作者：
H. Westphal
中科院分区：
文献类型：
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作者：
K. Mahon;P. Overbeek;H. Westphal
我们培育了一系列具有产前致死性的转基因小鼠。这些小鼠携带嵌合质粒，其中含有与氯霉素乙酰转移酶基因（pRSV-CAT）编码区相连的劳斯肉瘤病毒的长末端重复序列。 pRSV-CAT 整合位点杂合的小鼠是半不育的，当与正常小鼠杂交时，其产仔数大约等于平均大小的 40%。这种杂交产生的后代中大约 50% 带有 pRSV-CAT 序列，并且产生的窝数也较小。胚胎发生分析显示，植入的胚胎数量正常，但 60% 在第 7 天后未能发育。另外八个含有 RSV-CAT 的独立转基因品系没有显示胚胎致死的证据；因此，观察到的缺陷不太可能是由于 RSV-CAT 表达的直接影响造成的。我们发现携带者小鼠在 6 号和 17 号染色体之间存在相互易位，T(6A2-6A3;17D-17E1)，这可以解释该品系中所见的明显显性胚胎致死性。整合位点已通过原位杂交定位于易位染色体之一的易位断点处或附近(6(17))。由于外源 DNA 存在于其中一条易位染色体中，因此我们推测这种重排是由外源 DNA 的引入引起的。
We have produced a line of transgenic mice that is characterized by prenatal lethality. These mice bear a chimeric plasmid containing the long terminal repeat of the Rous sarcoma virus linked to the coding region of the chloramphenicol acetyltransferase gene (pRSV-CAT). Mice heterozygous for the pRSV-CAT integration site are semisterile, producing litters approximately equal to 40% of the average size when crossed to normal mice. Approximately 50% of the progeny from such a cross bear the pRSV-CAT sequences and also produce litters of smaller size. An analysis of embryogenesis revealed that normal numbers of embryos implanted, but 60% failed to develop past day 7. Eight other independent transgenic lines containing RSV-CAT show no evidence of embryonic lethality; thus, it is unlikely that the defect observed is due to the direct effects of RSV-CAT expression. We have found that carrier mice bear a reciprocal translocation between chromosomes 6 and 17, T(6A2-6A3;17D-17E1), that can explain the apparent dominant embryonic lethality seen in this line. The site of integration has been localized by in situ hybridization at or near the translocation breakpoint in one of the translocated chromosomes (6(17)). Because the foreign DNA is present in one of the translocated chromosomes, we propose that this rearrangement was elicited by the introduction of foreign DNA.