Cytokine genes single nucleotide polymorphism (SNP) screening analyses in canine malignant histiocytosis

Abstract

In humans, malignant histiocytosis is a tumour-like disease characterised by increasing proliferation of macrophages and reinforced degradation of erythrocytes. High progression of this disease leads to an unfavourable prognosis for the patients, most of them children up to the age of three years. Histological and cytological findings have proposed an important role of aberrant expression of cytokines in histiocytosis. Due to the fact that Bernese Mountain Dogs (BMD) show a predisposition for spontaneously developing malignant histiocytosis, these dogs could possibly be used as a genetic model organism to elucidate the mechanisms of human malignant histiocytosis. Canine cytokine cDNA transcripts of TNFalpha, Interleukin-1-alpha (IL-1alpha) and Interleukin-1-beta (IL-1beta) were screened for single nucleotide polymorphisms (SNPs). SNP screening in canine cytokine transcripts for malignant histiocytosis has not been carried out before. Total RNA was isolated from tissue samples from lung, spleen, testis and skin of 17 different dogs (fifteen BMDs, one Collie and one West Highland Terrier). The corresponding cytokine cDNAs were amplified, sequenced and then screened for SNPs. The resulting effects on the protein sequence were analysed. Several BMDs and the West Highland Terrier showed SNPs in the coding sequences which led to missense mutations within the protein sequences of TNFalpha, IL1alpha and IL1beta.