Genetic changes in methotrexate‐resistant mosquito cells

Frank A. Shotkoski, Ann Marie Fallon

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

A stepwise selection procedure was used to obtain from Mtx‐5011 Aedes albopictus cells, variants with increased resistance to methotrexate (mtx). On the basis of growth, the Mtx‐5011 derivatives were 270‐ to 3,000‐fold more resistant to mtx than wild‐type mosquito cells. Properties associated with mtx resistance in these cells were consistent with amplification of the dihydrofolate reductase (DHFR) gene. The cells overproduced DHFR protein, were enriched with DHFR mRNA, and DNA from resistant cells was enriched for a band that likely contained the DHFR coding sequence. Karyotype analysis indicated that high levels of resistance were accompanied by a conversion to tetraploidy, chromosome rearrangements, and an apparent duplication of one of the mosquito chromosomes.

Original languageEnglish (US)
Pages (from-to)79-92
Number of pages14
JournalArchives of Insect Biochemistry and Physiology
Volume15
Issue number2
DOIs
StatePublished - 1990

Keywords

  • Aedes albopictus
  • dihydrofolate reductase
  • gene amplification

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