Back to Search
Start Over
Expression of a methotrexate resistant dihydrofolate reductase gene in transgenic mice
- Source :
- Developmental Genetics. 10:349-355
- Publication Year :
- 1989
- Publisher :
- Wiley, 1989.
-
Abstract
- We have previously demonstrated systemic resistance to methotrexate (MTX) in transgenic mice carrying a foreign, mutant dihydrofolate reductase (DHFR, E.C. 1.5.1.3) gene. The new gene was introduced as a cDNA cloned into an expression vector driven by the simian virus 40 (SV40) early promoter. Previous physiologic studies suggested that transgenic mice tolerated drug doses invariably lethal to controls on the basis of gastrointestinal (GI) resistance to MTX. In the present study we evaluated foreign gene expression at the RNA level in the three major sites of MTX toxicity: intestine, liver, and bone marrow. The transgene was transcriptionally active in small bowel, and levels of expression were high in animals tolerating the largest doses of MTX. The gene was also expressed in the liver in some pedigrees, but was not detected in hemopoietic tissues of any of the pedigrees tested. Our studies correlate the site of expression of a drug resistant dhfr gene with an altered physiologic response to MTX, and demonstrate that transgenic mice can be used as a test system for expression of genes considered for use in somatic gene therapy.
- Subjects :
- Genetic enhancement
Transgene
Mutant
Drug Resistance
Gene Expression
Mice, Transgenic
Simian virus 40
Biology
Mice
Bone Marrow
Intestine, Small
Gene expression
Dihydrofolate reductase
Genetics
medicine
Animals
Promoter Regions, Genetic
Gene
Expression vector
Cell Biology
Molecular biology
Tetrahydrofolate Dehydrogenase
Methotrexate
Liver
Mutation
biology.protein
RNA
Electrophoresis, Polyacrylamide Gel
Plasmids
Developmental Biology
medicine.drug
Subjects
Details
- ISSN :
- 15206408 and 0192253X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Developmental Genetics
- Accession number :
- edsair.doi.dedup.....94fae59f07ee60196527ca3a10c1c748