The cattle interleukin-13 gene: genomic organization, chromosomal location, and evolution of the promoter

Interleukin (IL)-13 plays a key role in the T-helper 2 type immune response. In domestic animal species no sequence information is available for the IL13 gene. Here, we report the isolation and sequencing of the cattle IL13 gene. Since a heterologous cDNA probe failed to hybridize to cattle genomic DNA the gene was identified by a positional sequencing approach. In human and mouse both cytokines are located within a region of about 30 kilobases (kb). Therefore the region upstream of the cattle IL4 gene has been sequenced by a shotgun approach. The cattle IL13 gene was found to be located about 20 kb upstream of IL4 in a head-to-tail orientation. The exon-intron structure and the promoter region is well conserved across species. The alignment of the IL13 sequences from different species allowed the identification of highly conserved amino acid positions and transcriptional elements. Two conserved amino acid positions (glu(31) and pro(94)) are most probably homologous to the interleukin-4 signalling residues. One of the potential binding sites for transcription factors is located at position -197 to -189 and is closely related to the P elements of the IL4 promoter. Nevertheless, the overall identity of the promoter sequences of IL13 and IL4 is low. Therefore we conclude that both cytokines use diverse regulatory elements. There is evidence that IL-13, but not IL-14, is the key mediator in allergic asthma. Furthermore IL-13 is involved in resistance to some infections. Therefore IL-13 is of interest for disease association studies in domestic animals.