Mahon K A, Overbeek P A, Westphal H
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1988 Feb;85(4):1165-8. doi: 10.1073/pnas.85.4.1165.
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.
我们培育出了一系列具有产前致死特征的转基因小鼠。这些小鼠携带一种嵌合质粒，该质粒包含与氯霉素乙酰转移酶基因编码区相连的劳氏肉瘤病毒长末端重复序列（pRSV-CAT）。pRSV-CAT整合位点的杂合小鼠半不育，与正常小鼠杂交时产仔数约为平均大小的40%。这种杂交产生的后代中约50%携带pRSV-CAT序列，并且产仔数也较少。胚胎发生分析显示，植入的胚胎数量正常，但60%的胚胎在第7天之后无法发育。其他八个含有RSV-CAT的独立转基因品系未显示出胚胎致死的迹象；因此，观察到的缺陷不太可能是由于RSV-CAT表达的直接影响。我们发现携带小鼠在6号和17号染色体之间存在相互易位，即T(6A2-6A3;17D-17E1)，这可以解释该品系中明显的显性胚胎致死现象。通过原位杂交已将整合位点定位在其中一条易位染色体（6(17)）的易位断点处或附近。由于外源DNA存在于其中一条易位染色体中，我们推测这种重排是由外源DNA的引入引起的。
