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 anti-inflammatory and pro-inflammatory properties in various cellular and disease contexts. OSM signals through two receptor complexes, one of which includes OSMRb. Here, we investigated OSM-OSMRb signaling in adult mouse hematopoietic stem cells (HSCs) using the conditional Osmrfl/fl mouse model B6;129-Osmrtm1.1Nat/J. We crossed Osmrfl/fl mice to interferon-inducible Mx1-Cre, which is robustly induced in adult HSCs. From these mice, we isolated HSCs by flow cytometry, stimulated with or without recombinant OSM for 1 hour, and assessed gene expression changes in control versus Osmr knockout HSCs by RNA-seq. This data may be utilized to investigate OSMRb-dependent and -independent OSM signaling as well as the transcriptional effects of an IL-6 family cytokine on mouse HSCs to further define its anti-inflammatory versus pro-inflammatory properties. Overall design: We sought to assess levels of Osmr transcript and Osmr signaling in prospectively isolated hematopoietic stem cells (HSCs) from the bone marrow of mice using fluorescence-activated cell sorting (Lineage- Sca-1+ c-Kit+ Flt3- CD150+ CD48-). HSCs from Osmrfl/fl Mx1-Cre female mice (2-4 months of age) and control Mx1-Cre female mice (2-4 months of age) were placed into serum-free StemSpan SFEM II media with 100ng/ml SCF, 50ng/ml TPO, and with or without 500ng/mL of recombinant murine OSM 60min, then flash frozen for RNA sequencing (RNA-seq). Significantly differentially expressed genes were defined based on stringent cutoffs (p < 0.01 and log2(FC) > 2 or < -2). N= 3-6 mice per group, experiment done two independent times. UPDATE: [07-10-2024] The titles and characteristics of the Samples were updated. The associated data did not change.