Allele-specific expression patterns of interleukin-2 and Pax-5 revealed bya sensitive single-cell RT-PCR analysis

Autosomal genes that are subject to random allelic Inactivation (RAI), like imprinted genes [1] and genes subject to X-inactivation Gal, require mecha nisms that dictate the differential transcriptional regulation of two seque nce-identical alleles. RAI genes include olfactory receptor genes [3], and the various genes encoding antigen receptors on lymphocytes (immunoglobulin genes, T cell receptor genes and NK receptor genes [4-7]). These observati ons raise the possibility that other genes might be similarly regulated. Mo reover, an interesting possibility is that certain genes might be monoallel ically expressed in some cells and biallelically expressed in others. Recen tly, reports of monoallelic expression of interleukin-2 (IL-2) [8,9] and IL -4 [10,11] have raised the possibility that the cytokine gene family may be subject to monoallelic expression. Another report suggests that the gene e ncoding the transcription factor Pax-5, which is involved in B-cell (and ce rebellar) development [12,13], is also subject to monoallelic expression [1 4]. Using a novel single-cell reverse transcription-polymerase chain reacti on (RT PCR) approach, we have analyzed the IL-2 and Pax-5 genes in mice. We found that IL-2 is monoallelically transcribed in some T cells and biallel ically transcribed in others, raising interesting questions regarding cytok ine gene regulation. Additionally, our analyses suggest that Pax-5 is consi stently biallelically transcribed. Thus, the IL-2 gene and other cytokine g enes may be regulated in a stochastic manner that results in 0, 1 or 2 alle les of a given cytokine gene expressed in each T cell. This type of regulat ion could account for the wide variety of different combinations of cytokin e genes expressed in individual T cells and therefore plays a role in the g eneration of T cells with a range of different effector functions. (C) 2000 Elsevier Science Ltd. All rights reserved.