Long-term protection of recipient mice from lethal doses of methotrexate by marrow infected with a double-copy vector retrovirus containing a mutant dihydrofolate reductase Journal Article
| Authors: | Zhao, S. C.; Li, M. X.; Banerjee, D.; Schweitzer, B. I.; Mineishi, S.; Gilboa, E.; Bertino, J. R. |
| Article Title: | Long-term protection of recipient mice from lethal doses of methotrexate by marrow infected with a double-copy vector retrovirus containing a mutant dihydrofolate reductase |
| Abstract: | A double-copy Moloney murine leukemia virus-based retroviral construct containing both the NEOr gene and a mutated dihydrofolate reductase cDNA (Leu 22-->Arg) was used to infect mouse bone marrow cells. The infected mouse marrow was returned to lethally irradiated mice. Primary, secondary, and even tertiary recipients transplanted with bone marrow cells infected with the recombinant virus showed protection from lethal methotrexate toxicity. The viral construct containing a SV-40 promoter in the U3 region of the 3' long terminal repeat appeared to be more effective than a similar construct containing the adenosine deaminase promoter, although both afforded protection. Evidence for integration into blood cells of both the NEOr gene and the mutated dihydrofolate reductase gene was obtained by polymerase chain reaction; sequencing of the amplified dihydrofolate reductase cDNA showed the presence of the point mutation. These results indicate that early hematopoietic progenitor cells in the mouse can be successfully transduced with a drug resistance gene. |
| Keywords: | genetics; methotrexate; molecular genetics; mouse; animal; metabolism; mice; drug effect; drug resistance; transfection; genetic vectors; molecular sequence data; hybrid protein; genetic transfection; recombinant fusion proteins; nucleotide sequence; organ specificity; hematopoietic stem cells; reporter gene; base sequence; antibody specificity; genes, reporter; hematopoietic stem cell; mouse strain; mice, inbred cba; point mutation; dihydrofolate reductase; tetrahydrofolate dehydrogenase; bone marrow transplantation; moloney leukemia oncovirus; moloney murine leukemia virus; repetitive sequences, nucleic acid; nucleotide repeat; complementary dna; dna, complementary; virus dna cell dna interaction; virus integration; dna vector; article; radiation chimera; support, u.s. gov't, p.h.s. |
| Journal Title: | Cancer Gene Therapy |
| Volume: | 1 |
| Issue: | 1 |
| ISSN: | 0929-1903 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1994-03-01 |
| Start Page: | 27 |
| End Page: | 33 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 7621235 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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