Abstract
In the process of generating transgenic mice, inserted foreign DNA can cause insertional inactivation of the flanking genetic locus and simultaneously provide a molecular tag for localizing and cloning the inactivated gene. We describe the case of an insertional mutation leading, in animals homozygous for the insertion, to severe anaemia that was lethal within a few days after birth. The haemolytic anaemia and microspherocytosis of the red cells strongly suggested membrane abnormalities of the erythrocytes. By in situ localization of the integration site, protein analysis of the red cell membranes, northern and Southern blot analyses, we were able to demonstrate that the integrated transgene had affected the alpha-spectrin gene locus.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anemia, Hemolytic / genetics*
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Animals
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Animals, Newborn
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Blotting, Southern
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Chromosome Mapping
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Cloning, Molecular
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DNA / genetics
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DNA / isolation & purification
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DNA, Viral / administration & dosage
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DNA, Viral / genetics
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DNA, Viral / isolation & purification
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Erythrocyte Membrane / chemistry
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Erythrocytes / physiology
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Erythrocytes / ultrastructure
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Female
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Genes, tat*
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HIV-1 / genetics*
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Hemoglobins / genetics
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Hemoglobins / isolation & purification
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Homozygote
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Humans
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In Situ Hybridization
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Karyotyping
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Mice
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Mice, Transgenic
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Microscopy, Electron, Scanning
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Mutagenesis, Insertional*
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Restriction Mapping
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Simian virus 40 / genetics*
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Spectrin / genetics*
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Spherocytosis, Hereditary / genetics*
Substances
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DNA, Viral
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Hemoglobins
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Spectrin
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DNA