Abstract |
The analysis of spontaneous somatic mutants gives insights into the regulation of gene expression. Human heavy-chain disease (HCD) is a monoclonal lymphoproliferative disorder characterized by the presence of truncated immunoglobulin ( Ig) heavy chains without associated light chains. To better understand the molecular mechanisms leading to the loss of light-chain production, we have examined a murine cell line model of heavy-chain disease. R15, a spontaneous mutant of the IgA, kappa-producing myeloma cell line W3129, produces heavy chain but no light chain. The variant delta 15 derived from R15 resembles human HCD in that it secretes a shortened heavy chain with no associated light chain. Cloning and analysis of the R15 kappa light-chain gene revealed that a 358-nucleotide insertion of unknown origin replaced 22 bases of the wild-type leader-variable region (L-V) intron (IVS). Although this genomic change left the light-chain exons and known regulatory elements intact, it altered the mRNA processing pathway, yielding two alternative RNA products, neither of which encodes a functional protein. This mutant therefore provides new insights into how genomic changes can influence gene expression.
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Authors | C L Chou, S L Morrison |
Journal | Somatic cell and molecular genetics
(Somat Cell Mol Genet)
Vol. 19
Issue 2
Pg. 131-9
(Mar 1993)
ISSN: 0740-7750 [Print] United States |
PMID | 8511672
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Immunoglobulin kappa-Chains
- RNA, Messenger
- DNA
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Topics |
- Animals
- Base Sequence
- Blotting, Northern
- Blotting, Southern
- Cloning, Molecular
- DNA
- Heavy Chain Disease
(genetics)
- Humans
- Immunoglobulin kappa-Chains
(genetics)
- Mice
- Molecular Sequence Data
- Mutation
- RNA, Messenger
(metabolism)
- Restriction Mapping
- Tumor Cells, Cultured
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