RABBIT ALLOTYPES--STRUCTURE, ORGANIZATION AND REGULATED EXPRESSION OF IG GENES

我们寻找一种分子解释来解释基因表达缺失的原因

We sought a molecular explanation for the loss of expression of the normally predominant K1-b9 type of kappa light chains in Basilea rabbits. No major deletions or rearrangements associated with Ckappa1 were found by Southern analyses. We cloned and sequenced the Ckappa1 gene and its 3' and 5' flanking regions and found a G to A transition in the acceptor splice site of the Jkappa-Ckappa intron. This change in an invariant AG/ to AA/ provides a molecular explanation for the loss of K1 light chain expression. We cloned and sequenced VH genes from a rabbit of a3 phenotype in an attempt to understand the molecular basis for serological observations of latent VHa allotype expression. We found rabbit VH genes that were unusually close (approximately 3kb apart) and encoded unusual combinations of allotype-correlated codons. It now appears unlikely that all rabbits have the same genomic content of structural genes for VH regions or that the allelic behavior of VH allotypes simply reflects regulatory genes. Since most alternative amino acids at allotype-correlated positions can be derived from each other by single-base changes, somatic mutations and/or gene-conversion-like events may explain at least some observations of latent VHa allotypes. The proximity of rabbit VH genes may enhance gene-conversion-like events. We cloned and sequenced two thymus-derived cDNA clones that encode the constant region of the rabbit T cell receptor Beta chain and found high homology to the human and murine sequences. One cDNA encodes an unusual non-VBeta sequence 5' of CBeta that would produce a protein with unknown function. The other encodes a rabbit VBeta with 72.5% homology to a mouse VBeta. In addition, the sequence of a corresponding single-copy genomic VBeta from a second rabbit had an identical sequence suggesting that no somatic mutations have occurred in the expressed VBeta gene.