C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo

Abstract

<b>Background</b>: Infections cause the production of inflammatory cytokines such as Interferon gamma (IFNγ). IFNγ in turn prompts the upregulation of a range of host defence proteins including members of the family of guanylate binding proteins (Gbps). In humans and mice alike, GBPs restrict the intracellular replication of invasive microbes and promote inflammation. To study the physiological functions of Gbp family members, the most commonly chosen <i>in vivo</i> models are mice harbouring loss-of-function mutations in either individual <i>Gbp</i> genes or the entire <i>Gbp</i> gene cluster on mouse chromosome 3. Individual <i>Gbp</i> deletion strains differ in their design, as some strains exist on a pure C57BL/6 genetic background, while other strains contain a 129-derived genetic interval encompassing the <i>Gbp</i> gene cluster on an otherwise C57BL/6 genetic background. <b>Methods</b>: To determine whether the presence of 129 alleles of paralogous <i>Gbps</i> could influence the phenotypes of 129-congenic <i>Gbp</i>-deficient strains, we studied the expression of Gbps in both C57BL/6J and 129/Sv mice following <i>in vivo</i> stimulation with adjuvants and after infection with either <i>Toxoplasma</i> <i>gondii</i> or <i>Shigella flexneri</i>. <b>Results</b>: We show that C57BL/6J relative to 129/Sv mice display moderately elevated expression of Gbp2, but more prominently, are also defective for Gbp2b (formerly Gbp1) mRNA induction upon immune priming. Notably, <i>Toxoplasma</i> infections induce robust Gbp2b protein expression in both strains of mice, suggestive of a <i>Toxoplasma</i>-activated mechanism driving Gbp2b protein translation. We further find that the higher expression of Gbp2b mRNA in 129/Sv mice correlates with a gene duplication event at the <i>Gbp2b</i> locus resulting in two copies of the <i>Gbp2b</i> gene on the haploid genome of the 129/Sv strain. <b>Conclusions</b>: Our findings demonstrate functional differences between 129 and C57BL/6 <i>Gbp</i> alleles which need to be considered in the design and interpretation of studies utilizing mouse models, particularly for phenotypes influenced by Gbp2 or Gbp2b expression.