Characterization of an Osmr Conditional Knockout Mouse Model

Oncostatin M (OSM) is a member of the interleukin-6 (IL-6) family of cytokines and has been found to have distinct anti-inflammatory and pro-inflammatory properties in various cellular and disease contexts. OSM signals through two receptor complexes, one of which includes OSMRβ. To investigate OSM-OSMRβ signaling in adult hematopoiesis, we utilized the readily available conditional Osmr(fl/fl) mouse model B6;129-Osmr(tm1.1Nat)/J, which is poorly characterized in the literature. This model contains loxP sites flanking exon 2 of the Osmr gene. We crossed Osmr(fl/fl) mice to interferon-inducible Mx1-Cre, which is robustly induced in adult hematopoietic cells. We observed complete recombination of the Osmr(fl) allele and loss of exon 2 in hematopoietic (bone marrow) as well as non-hematopoietic (liver, lung, kidney) tissues. Using a TaqMan assay with probes downstream of exon 2, Osmr transcript was lower in the kidney but equivalent in bone marrow, lung, and liver from Osmr(fl/fl) Mx1-Cre versus Mx1-Cre control mice, suggesting that transcript is being produced despite loss of this exon. Western blots show that liver cells from Osmr(fl/fl) Mx1-Cre mice had complete loss of OSMR protein, while bone marrow, kidney, and lung cells had reduced OSMR protein at varying levels. RNA-seq analysis of a subpopulation of bone marrow cells (hematopoietic stem cells) finds that some OSM-stimulated genes, but not all, are suppressed in Osmr(fl/fl) Mx1-Cre cells. Together, our data suggest that the B6;129-Osmr(tm1.1Nat)/J model should be utilized with caution as loss of Osmr exon 2 has variable and tissue-dependent impact on mRNA and protein expression.