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An insertion-deletion event in murine immunoglobulin kappa gene resembles mutations at heavy-chain disease loci.
- Source :
-
Somatic cell and molecular genetics [Somat Cell Mol Genet] 1993 Mar; Vol. 19 (2), pp. 131-9. - Publication Year :
- 1993
-
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.
Details
- Language :
- English
- ISSN :
- 0740-7750
- Volume :
- 19
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Somatic cell and molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 8511672
- Full Text :
- https://doi.org/10.1007/BF01233529