A Point Mutation in Suppressor of Cytokine Signalling 2 (Socs2) Increases the Susceptibility to Inflammation of the Mammary Gland while Associated with Higher Body Weight and Size and Higher Milk Production in a Sheep Model

• DOI: 10.1371/journal.pgen.1005629
• Publication Date: 2015-12-14T17:58:15Z
• Authors: Rachel Rupp; Pavel Senin; Julien Sarry; Charlotte Allain; Christian Tasca; Laeticia Ligat; David Portes; Florent Woloszyn; Olivier Bouchez; Guillaume Tabouret; Mathieu Lebastard; Cécile Caubet; Gilles Foucras; Gwenola Tosser-Klopp
• Keywords: SOCS2

Mastitis is an infectious disease mainly caused by bacteria invading the mammary gland. Genetic control of susceptibility to mastitis has been widely evidenced in dairy ruminants, but genetic basis and underlying mechanisms are still largely unknown. We describe discovery, fine mapping functional characterization a variant associated with elevated milk leukocytes count, or SCC, as proxy for mastitis. After implementing genome-wide association studies, we identified major QTL SCC on ovine chromosome 3. Fine region, using full sequencing 12X coverage three animals, provided one strong candidate SNP that mapped coding sequence highly conserved gene, suppressor cytokine signalling 2 (Socs2). The frequency increased was 21.7% Socs2 genotype explained 12% variance trait. point mutation induces p.R96C substitution SH2 domain SOCS2 i.e. binding site protein various ligands, well-established growth hormone receptor GHR. Using surface plasmon resonance showed completely abrogates affinity phosphopeptide Additionally, size, weight production homozygote sheep, were significantly 24%, 18%, 4.4%, respectively, when compared wild type supporting view causes loss activity. Altogether these results provide evidence causal controlling sheep highlight role tradeoff between host's inflammatory response infections, body production, which all mediated JAK/STAT signaling pathway.