Oral Presentation International Veterinary Immunology Symposium 2016

Identification of a SOCS-2 point mutation and its role on immune responsiveness and predisposition to mastitis in dairy sheep (#76)

Gilles FOUCRAS 1 , Rachel RUPP 2 , Guillaume TABOURET 1 , Olivier BOUCHEZ 3 , Gwenola TOSSER-KLOPP 2
  1. IHAP, INRA, ENVT, Toulouse Cedex 03, FR, France
  2. GenPhySE, INRA, ENSAT, ENVT, Toulouse, France
  3. GeT-PlaGe, GenoToul, Toulouse, France

Mammary inflammation is mainly caused by extracellular bacteria upon colonisation through the teat canal. Genetic control of susceptibility to mastitis has been widely evidenced in dairy ruminants, but the genetic basis is still largely unknown. Elevated milk somatic cell count (SCC) is a good indicator of mastitis, and is recorded on a large scale. Through a genome-wide association study using SCC as a proxy, we identified a major QTL on ovine chromosome 3. Genome sequencing of segregating rams led to the identification of one non-synonymous mutation in Suppressor Of Cytokine Signalling 2 (Socs2). The mutation frequency established by a KASPar assay is 22% in the discovery population. Furthermore, Socs2 genotype explains 12% of the SCC variance. The R96C mutation is in the Sarc-homology domain, which is the binding site of SOCS-2 to various hormones and cytokines receptors. Using surface plasmon resonance, we showed that the point mutation is associated with a loss of function. Socs2 knock-out mice have a high-growth phenotype. Indeed, size and weight showed a significant difference of respectively +24% and +18% between homozygote R96C and wild type half-sib mates. To further investigate the link between Socs2 genotypes and failure of mammary response to infection, a whole blood transcriptome by RNA-sequencing was performed on six ewes of each of the two homozygote Socs2 genotypes. Differentially-expressed genes indicated a significant alteration of the type I interferon signalling pathway. Further, when cytokine gene expression was measured upon stimulation with heat-killed Staphylococcus aureus, a frequent mastitis pathogen in sheep, IL-17 expression was shown to be altered in relation with the presence of the SOCS-2 point mutation. Altogether these results provide strong evidence that besides milk production, weight and stature and a possible altered trade-off between functions, SOCS2 controls the host’s inflammatory response to mammary infections in dairy ruminants.