Characterization of the divergent eosinophil ribonuclease, mEar 6, and its expression in response to Schistosoma mansoni infection in vivo

Genes Immun. 2004 Dec;5(8):668-74. doi: 10.1038/sj.gene.6364143.

Abstract

The eosinophil-associated ribonucleases (Ears) are rapidly evolving proteins found in multigene clusters that are unique to each rodent species. Of the 15 independent genes in the Mus musculus cluster, only mEars 1 and 2 are expressed at significant levels at homeostasis. Here we characterize the expression of mEar 6 in the liver and spleen in mice in response to infection with the helminthic parasite, Schistosoma mansoni. Interestingly, expression of mEar 6 is not directly related to the elevated levels of serum IL-5 or tissue eosinophilia characteristic of this disease, as no mEar 6 transcripts were detected in the liver or the spleen from uninfected IL-5-transgenic mice. The coding sequence of mEar 6 has diverged under positive selection pressure (K(a)/K(s) > 1.0) and has a unique unpaired cysteine near the carboxy-terminus of the protein. The high catalytic efficiency of recombinant mEar 6 (k(cat)/K(m) = 0.9 x 10(6)/M/s) is similar to that of the cluster's closest human ortholog, eosinophil-derived neurotoxin (EDN/RNase 2). In summary, we have identified mEar 6 as one of only two RNase A superfamily ribonucleases known to be expressed specifically in response to pathophysiologic stress in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • DNA Primers
  • Eosinophil Cationic Protein / genetics*
  • Eosinophil Cationic Protein / metabolism
  • Evolution, Molecular
  • Gene Expression*
  • Immunoblotting
  • Liver / metabolism
  • Liver / pathology
  • Mice
  • Molecular Sequence Data
  • Recombinant Proteins / metabolism
  • Schistosoma mansoni*
  • Schistosomiasis mansoni / genetics
  • Schistosomiasis mansoni / metabolism*
  • Schistosomiasis mansoni / pathology
  • Selection, Genetic
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Spleen / metabolism
  • Spleen / pathology

Substances

  • DNA Primers
  • Recombinant Proteins
  • Eosinophil Cationic Protein