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PMID: 3097643 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Structural differences in a single gene encoding the V kappa Ser group of light chains explain the existence of two mouse light-chain genetic markers.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 23 ·1986-12-00 ·Pages 9134-8

Boyd RT, Goldrick MM, Gottlieb PD

Abstract

Two phenotypic markers of mouse immunoglobulin kappa light chains, the IB-peptide marker and the Ef1a isoelectric focusing marker, are expressed by the C58/J, AKR/J, RF/J, and PL/J strains (called expressor strains) but not by BALB/c and most inbred strains. Expression is linked to the kappa light-chain locus and the Lyt-2/Lyt-3 genes on chromosome 6. Light chains bearing these markers belong to a group of variable region kappa chain (V kappa) regions called V kappa Ser, which has a serine amino terminus and a framework 1 region not observed to date among BALB/c light chains. Southern hybridization of genomic DNA with a V kappa Ser-specific cDNA probe has demonstrated a single strongly hybridizing DNA fragment in all strains of mice tested. Characteristic restriction enzyme polymorphisms define the V kappa Ser alleles of expressor (Igk-VSera) and nonexpressor (Igk-VSerb) strains. In the present study, the unrearranged V kappa Ser gene and its flanking regions from an expressor (C.C58) and nonexpressor (BALB/c) strain have been cloned and their nucleotide sequences determined. The C.C58 V kappa Ser gene isolated (the Igk-VSera allele) was shown to code for the two phenotypic markers described. While the nucleotide sequence of the BALB/c coding region (the Igk-VSerb allele) shows 97% identity with the C.C58 gene, single nucleotide substitutions lead to structural changes in the encoded protein which render it IB-negative and Ef1a-negative. These differences alone can explain the failure of strains containing the BALB/c allele to express these kappa-chain phenotypic markers. Also, the BALB/c gene contains a single substitution in a conserved octamer sequence approximately equal to 100 nucleotides upstream of the coding region, which could affect its expression. Finally, the C.C58 allele contains a BAM5/R repetitive DNA element approximately equal to 1200 nucleotides upstream of the coding regions that is not present in BALB/c. This element gives rise to the EcoRI and BamHI restriction enzyme polymorphisms, which distinguish the Igk-VSera and Igk-VSerb alleles.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cloning, Molecular Gene Expression Regulation Genes Immunoglobulin Variable Region/genetics Immunoglobulin kappa-Chains/genetics Mice Mice, Inbred Strains/genetics Polymorphism, Genetic Sequence Homology, Nucleic Acid
Chemicals
Immunoglobulin Variable Region Immunoglobulin kappa-Chains
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Boyd R T
Goldrick M M
Gottlieb P D
References (42)
42 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.83.23.9134
Published
1986-12-00
Pages
9134-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC387089
Subset
IM
Grants
NCI NIH HHS · CA30147 · United States
Databases
GENBANK
M14360, M14361
External Links
PubMed source DOI: 10.1073/pnas.83.23.9134 PMC Full Text View journal details
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