| First Author | Pravtcheva DD | Year | 1995 |
| Journal | Genomics | Volume | 30 |
| Issue | 3 | Pages | 529-44 |
| PubMed ID | 8825640 | Mgi Jnum | J:30581 |
| Mgi Id | MGI:78080 | Doi | 10.1006/geno.1995.1274 |
| Citation | Pravtcheva DD, et al. (1995) A postimplantation lethal mutation induced by transgene insertion on mouse chromosome 8. Genomics 30(3):529-44 |
| abstractText | We have produced three lines of transgenic mice that contain additional copies of the mouse phosphoglycerate kinase 1 (Pgk1) gene. Two of these lines, 94-A and 94-K, which are descendants of a common founder, did not produce liveborn progeny carrying two copies of these transgenes (i.e., A/A, K/K, or A/K). Genotyping of midgestation embryos showed that A/K embryos are dead by Embryonic Day 10. Comparison of the level of transgene expression in the three transgenic lines ruled out PGK1 toxicity as the cause of death of A/A, A/K, and WK embryos. The death of A/ A, K/K, and A/K transgenic mice was therefore attributed to an insertional mutation disrupting a gene or genes essential for normal embryogenesis. Analysis of the structure of the 94-A and 94-K transgenes indicated that they differ in the number of tandem repeats and in the positions of the transgene-cellular DNA junctions. To determine if the two transgenes represent a single integration followed by a rearrangement or two independent integration events, we cloned the endogenous sequences surrounding the 94-A and 94-K transgene insertion sites. Restriction analysis of the isolated genomic clones indicated that the endogenous sequences abutting the 3' ends of the 94-A and 94-K transgenes are separated by less the 20 kb, providing strong support for the single integration model. Further analysis indicated that the 94- A transgene is associated with a deletion of at least 18 kb and is located in the vicinity of a widely transcribed endogenous gene. Chromosomal mapping of the endogenous sequences flanking the 94-A and 94-K transgene insertions using mouse-hamster somatic cell hybrids and a (C57BL/6J x SPRET/Ei)F1 x SPRET/Ei backcross panel allowed us to assign the 94-A(K) transgene insertion to the subcentral region of mouse chromosome 8. (C) 1995 Academic Press, Inc. |
