An insertion-deletion event in murine immunoglobulin kappa gene resembles mutations at heavy-chain disease loci.

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.

• 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.)

Chemical References

• Immunoglobulin kappa-Chains
• RNA, Messenger
• DNA

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