Wagner E F, Covarrubias L, Stewart T A, Mintz B
Cell. 1983 Dec;35(3 Pt 2):647-55. doi: 10.1016/0092-8674(83)90097-1.
The mutagenic potential of recombinant DNA in the germ line was investigated in the descendants of mice obtained from eggs injected with the human growth-hormone gene in a pBR322 vector. Six positive animals (including one mosaic) were produced and had 1-20 copies of the donor sequences in unique and often complex integration patterns indicative of a single or an interrupted insertion. All were heterozygotes and transmitted the foreign insert to their progeny, forming six new HUGH strains. Matings between heterozygotes yielded viable healthy homozygotes in four of the strains. However, in the HUGH/3 and HUGH/4 strains, no postnatal homozygotes were found and litter sizes at birth were small. These two independent cases of mutation, both homozygous recessive prenatal lethals, are attributable to disruption of native sequences by alien ones. They constitute the first instances of insertional mutagenesis due to integration of recombinant DNA in the germ line of the mouse. The mutants provide new possibilities for molecular identification of gene functions necessary for normal development.
在从注射了携带人生长激素基因的pBR322载体的卵子所获得的小鼠后代中，研究了生殖系中重组DNA的诱变潜力。产生了6只阳性动物（包括1只嵌合体），它们具有1至20个供体序列拷贝，呈独特且往往复杂的整合模式，表明存在单个或中断插入。所有动物均为杂合子，并将外源插入片段传递给后代，形成了6个新的HUGH品系。杂合子之间的交配在4个品系中产生了存活的健康纯合子。然而，在HUGH/3和HUGH/4品系中，未发现出生后的纯合子，且出生时的窝仔数较少。这两个独立的突变案例均为纯合隐性产前致死，是由于外来序列破坏了天然序列所致。它们构成了由于重组DNA整合到小鼠生殖系中而导致插入诱变的首例。这些突变体为正常发育所需基因功能的分子鉴定提供了新的可能性。
