Allotypes in Basilea rabbits

Weiß, Siegfried; García, Irene; Jaton, Jean‐Claude; Kelus, A. S.

doi:10.1002/eji.1830120213

Cited by 8 publications

(3 citation statements)

References 29 publications

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“…Recently, a Basilea strain of rabbit has been developed that expresses low amounts of bas K light chains and exhibits compensatory production of X light chains (4). Experiments from four laboratories indicate that bas is an isotypic form of rabbit K (K2) (5)(6)(7)(8)(9)(10). These and earlier observations of latent (unexpected) allotype expression have led to proposals that rabbit K allotypes are in fact isotypes whose expression is regulated in allelic fashion (11)(12)(13)(14).…”

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confidence: 99%

Kappa-chain allotypes and isotypes in the rabbit: cDNA sequences of clones encoding b9 suggest an evolutionary pathway and possible role of the interdomain disulfide bond in quantitative allotype expression.

McCartney-Francis¹,

Skurla²,

Mage³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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The constant regions of rabbit K light chains are unusual because the sequences of the allotypic forms can differ more from each other than do some variable regions with which they associate. We report the nucleic acid sequence of a full-length cDNA clone of b9 allotype and show comparisons to available sequences of the rabbit K allotypes b, b5, and bas-N4. Our analyses suggest that the primordial rabbit K gene encoded a bas-like sequence. They also reveal a surprising difference in the position of the variable region cysteine that forms the interdomain disulfide bond that is unique to most rabbit K chains. One b9 cDNA sequence lacks the usual cysteine-80 and instead encodes cysteine-108, which in three-dimensional models appears capable of forming the interdomain disulfide bond with cysteine-171 in the constant region. A partial sequence of a second b9 clone encodes both cysteine-80 and cysteine-108; the translation product of this clone could have a free reactive sulfitydryl group that might lead to an unstable nonfunctional Ig molecule. The fact that pre-B cells with b9 K chains do not differentiate and expand into productive Ig-producing cells with frequencies comparable to the other allotypes may be explained if a substantial proportion of the gene products have a free sulfhydryl group. Our sequence results suggest that in cells differentiating to produce K light chains of b9 allotype the number and location of the cysteines influence immunoglobulin expression.

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mentioning

confidence: 99%

Kappa-chain allotypes and isotypes in the rabbit: cDNA sequences of clones encoding b9 suggest an evolutionary pathway and possible role of the interdomain disulfide bond in quantitative allotype expression.

McCartney-Francis¹,

Skurla²,

Mage³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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“…The donor sites of x 1 b9 genes are inferred from the sequence of normal K 1 b9 cDNA (17). been detected serologically by inhibition assays (43). The b9 inhibitory activity in sera was not found on functional antibodies in rabbits producing anti-SII antibodies (43).…”

Section: Discussion the Basilea Strain Was Developed From A Mutant Ramentioning

confidence: 99%

“…been detected serologically by inhibition assays (43). The b9 inhibitory activity in sera was not found on functional antibodies in rabbits producing anti-SII antibodies (43). Possible sources of such light chains would be through some frameshift correction mechanism, through splicing to a cryptic acceptor site upstream of C~ in the J-C intron or downstream within the C, sequence, or less likely, through somatic back-mutation of the A to G.…”

Section: Discussionmentioning

confidence: 99%

Lack of K1b9 light chains in Basilea rabbits is probably due to a mutation in an acceptor site for mRNA splicing.

Lamoyi¹,

Mage²

1985

The Journal of Experimental Medicine

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Four forms of r immunoglobulin chains, known as the b4, b5, b6, and b9 allotypes, are products of allelic genes at the r 1 locus in domestic rabbit populations (1). A gene (K2) for a second r chain isotype (K2) is apparently present in all rabbits (2-5); one allotypic form of this gene is expressed at low levels in wild rabbits and some rabbits of b9 allotype (6-10). The Basilea strain was developed by Kelus and Weiss (11) from such a b9 rabbit in which an apparent mutation resulted in failure to produce the major type of Ig K light chains (K1). In these rabbits, the majority of Ig bear ~, light chains, and a small proportion bear r chains of the second isotype (K2) (8,(11)(12)(13). To understand the unusual r chain expression in Basilea rabbits, we have undertaken an analysis of the r genes in these animals. This report describes our investigations of the molecular basis for the loss of expression of K1 chains in the Basilea mutant.Rabbits are unusual in that they have two constant region r chain (C,) 1 genes (4, 5, 14-16). Although they have not yet been physically linked (4), the ~1 and ~2 genes are transmitted as linked traits in breeding colonies, and thus far no recombinants have been observed (6, 7, 9-11). The rl and r2 genes each have their own J (joining region) clusters (3, 5, 15). However, it is not known whether both Ca genes associate with the same variable region K chain (V~) gene pool. CK 1 genes show extensive polymorphism. Although the allelic b allotypes were first defined by serological and chemical analyses, the polymorphisms have now been studied by DNA sequencing (reviewed in l, 16-18). The DNA sequence homologies of the portions encoding K1 constant regions (C,1) range from 79% (b5 to b9) to 86% (b4 to b5) (16, 17). The known C~2 sequences are most similar to C,1 b9 (~89% homology) (17, 18). We used probes from the previously characterized cDNA (5, 18) and genomic clones to show, by Southern hybridization and restriction mapping, that both ~ 1 and K2 genes are present in DNA of Basilea rabbits, and that there are no detectable gross insertions, deletions, or other rearrangements in the K1 gene. For a finer analysis, we isolated and sequenced the mutant rlb9 gene. We found a G ~ A change in the highly conserved AG dinucleotide of the 3' acceptor splice site of the J-C intron. This substitution at ~ Abbreviations used in this paper: C, constant region; IVS, intervening sequence; J, joining region; SSC, saline sodium citrate; SDS, sodium dodecyl sulfate; UT, untranslated region; V, variable region; Y, pyrimidine.

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Genetics and expression of kappa-type light chains in Basilea rabbits

et al. 1984

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In contrast to rabbits of b4, b5, b6, and b9 allotypes whose serum immunoglobulins (Igs) are predominantly composed of kappa-type light chains, rabbits of the mutant Basilea strain have serum Igs that are largely of lambda type. We prepared several antisera that recognized a minor K2 (bas) light chain that is produced by Basilea rabbits. With these antisera we identified the K2 (bas) isotype in the serum of the original b9/b9 male rabbit whose offspring displayed the Basilea mutant phenotype. It was present in one half of his nonmutant offspring which inherited b9 from him and another b allotype from their mothers. Breeding was conducted both in Basel and at the NIH to develop and maintain colonies of mutant Basilea strain rabbits. The data obtained during colony development confirm that the trait of expression of the bas allotype maps to the same genetic region (b locus) that is known to control the allelic b allotypes b4, b5, b6 and b9. Homozygotes or heterozygotes of b4, b5 or b6 allotype (bb/bb) were mated with homozygous bbas / bbas rabbits to produce F1s , and then F2s as well as progeny of backcrosses to both homozygous parental types (bb/bb and bbas / bbas ) were produced. The bas allotype segregates as an allele (or pseudoallele ) at the b locus although there was a deficiency in recovery of homozygous bas offspring in both the F2 and backcross matings to bbas / bbas parental type in the NIH colony. This selective deficiency may reflect a deleterious effect on survival of homozygous bas progeny.

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Allotypes in Basilea rabbits

Cited by 8 publications

References 29 publications

Kappa-chain allotypes and isotypes in the rabbit: cDNA sequences of clones encoding b9 suggest an evolutionary pathway and possible role of the interdomain disulfide bond in quantitative allotype expression.

Kappa-chain allotypes and isotypes in the rabbit: cDNA sequences of clones encoding b9 suggest an evolutionary pathway and possible role of the interdomain disulfide bond in quantitative allotype expression.

Lack of K1b9 light chains in Basilea rabbits is probably due to a mutation in an acceptor site for mRNA splicing.

Genetics and expression of kappa-type light chains in Basilea rabbits

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