Organization of genes and spacers within the mouse immunoglobulin V(H) locus

D. J. Kemp, B. Tyler, O. Bernard, N. Gough, S. Gerondakis, J. M. Adams, S. Cory

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The germline organization of mouse immunoglobulin V[H] genes has been investigated using cloned V[H] sequences. Hybridization studies with V[H] probes fom plasmacytomas HPC76 (H76), S107, HOPC1 (H1), and lymphoma ABLS-8 (A8) demonstrated that the V[H] locus contains at least three distinct V[H] gene families. Comparison with other results suggests a total of about 10 such families, and of the order of 160 germline V[H] genes. Nucleotide sequencing revealed that the H76 family includes anti-inulin V[H] sequences, and the S107 family is known to encode antiphosphorylcholine sequences. The three V[H] gene families studied were mapped in the order H76-S107-A8/H1-C[H] by determining which V[H] genes had been deleted from several plasmacytomas by V[H] rearrangement events. Nine genomic clones from the H76 family, and one each from the S107 and A8/H1 families, were characterized; collectively they span 103 kilobases (kb). Two clones from the H76 family and one from the S107 family each bore a pair of V[H] genes separated by ~14 kb, suggesting that related V[H] genes in these families are clustered with a typical spacing of ~14 kb. No other V[H] genes were detected within the spacers, arguing against intermingling of different families. Within the V[H76] family cluster, however, two closely homologous V[H] genes were shown not to be adjacent. While spacer sequences were strongly conserved in the A8/H1 family, the H76 family had minimal conservation and that was restricted to regions immediately surrounding the genes. Hence conservaton of spacer sequences cannot be essential for V[H] gene function, nor for maintenance of a V[H] family. Spacers in both the H76 and S107 family contained small repeat elements, some of which behaved like mobile DNA sequences.

Original languageEnglish
Pages (from-to)245-261
Number of pages17
JournalJournal of Molecular and Applied Genetics
Issue number3
Publication statusPublished - 1 Dec 1981
Externally publishedYes

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