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Anemia in a line of transgenic mice carrying a mutant dihydrofolate reductase gene

Anemia in a line of transgenic mice carrying a mutant dihydrofolate reductase gene Several lines of transgenic mice were produced by pronuclear injection of a full‐length cDNA encoding a mutant dihydrofolate reductase (DHFR, E.C. 1.5.1.3). The mutation causes altered enzyme kinetics for folate reduction as well as low affinity for methotrexate (MTX). One line of mice carrying the plasmid displays a moderate‐to‐severe anemia that is evident in fetuses and newborn mice and that moderates with age. RNA studies revealed high levels of transcription of the mutant gene in the fetal and adult liver, and low or absent expression in adult bone marrow. Transcription of the mutant gene was not found in the fetal liver of other pedigrees examined. The data thus suggest that expression of this mutant gene in the main hematopoietic organ of the fetus adversely affects erythropoiesis by altering the cellular environment for erythroid differentiation, and that translocation of the site of hematopoiesis to bone marrow, where the foreign gene is not expressed, leads to normalization of red cell production. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Genesis: the Journal of Genetics and Development Wiley

Anemia in a line of transgenic mice carrying a mutant dihydrofolate reductase gene

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References (24)

Publisher
Wiley
Copyright
"Copyright © 1988 Wiley Subscription Services, Inc., A Wiley Company"
ISSN
1526-954X
eISSN
1526-968X
DOI
10.1002/dvg.1020090304
pmid
3409557
Publisher site
See Article on Publisher Site

Abstract

Several lines of transgenic mice were produced by pronuclear injection of a full‐length cDNA encoding a mutant dihydrofolate reductase (DHFR, E.C. 1.5.1.3). The mutation causes altered enzyme kinetics for folate reduction as well as low affinity for methotrexate (MTX). One line of mice carrying the plasmid displays a moderate‐to‐severe anemia that is evident in fetuses and newborn mice and that moderates with age. RNA studies revealed high levels of transcription of the mutant gene in the fetal and adult liver, and low or absent expression in adult bone marrow. Transcription of the mutant gene was not found in the fetal liver of other pedigrees examined. The data thus suggest that expression of this mutant gene in the main hematopoietic organ of the fetus adversely affects erythropoiesis by altering the cellular environment for erythroid differentiation, and that translocation of the site of hematopoiesis to bone marrow, where the foreign gene is not expressed, leads to normalization of red cell production.

Journal

Genesis: the Journal of Genetics and Development – Wiley

Published: Jan 1, 1988

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