Osmr-KO Mouse

Osmr, the Oncostatin M receptor, is a crucial component of the interleukin-6 (IL-6) family cytokine signaling. It forms functional receptor complexes with the common signal-transducing component glycoprotein 130 (gp130) and can bind Oncostatin M (OSM), playing a role in various biological processes [3]. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying Osmr's functions.

In pancreatic ductal adenocarcinoma (PDA), macrophage-secreted OSM activates Osmr in cancer-associated fibroblasts, reprogramming them to create a pro-tumourigenic environment. Tumour cells in Osm-deficient mice show reduced growth and metastasis [1]. In cardiac hypertrophy, Osmr deficiency aggravates the condition by modulating macrophages and the OSM/LIFR/STAT3 signalling pathway [2]. In glioblastoma, Osmr controls glioma stem cell respiration and confers resistance to ionizing radiation, and deletion of Osmr sensitizes these cells to radiation-induced death [5]. In primary localized cutaneous amyloidosis, OSMR mutations lead to elevated AHNAK expression, causing keratinocyte hyperproliferation and overdifferentiation [4].

In conclusion, Osmr plays essential roles in various disease-related biological processes, as revealed by model-based research. Osmr KO/CKO mouse models have contributed to understanding its role in diseases like PDA, cardiac hypertrophy, glioblastoma, and primary localized cutaneous amyloidosis, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Lee, Brian Y, Hogg, Elizabeth K J, Below, Christopher R, Valle, Juan W, Jørgensen, Claus. 2021. Heterocellular OSM-OSMR signalling reprograms fibroblasts to promote pancreatic cancer growth and metastasis. In Nature communications, 12, 7336. doi:10.1038/s41467-021-27607-8. https://pubmed.ncbi.nlm.nih.gov/34921158/

2. Feng, Yizhou, Yuan, Yuan, Xia, Hongxia, Shen, Difei, Tang, Qizhu. 2023. OSMR deficiency aggravates pressure overload-induced cardiac hypertrophy by modulating macrophages and OSM/LIFR/STAT3 signalling. In Journal of translational medicine, 21, 290. doi:10.1186/s12967-023-04163-x. https://pubmed.ncbi.nlm.nih.gov/37120549/

3. Lantieri, Francesca, Bachetti, Tiziana. 2022. OSM/OSMR and Interleukin 6 Family Cytokines in Physiological and Pathological Condition. In International journal of molecular sciences, 23, . doi:10.3390/ijms231911096. https://pubmed.ncbi.nlm.nih.gov/36232392/

4. Liu, Huiting, Qiu, Biying, Yang, Huan, Liu, Jun, Yang, Bin. 2023. AHNAK, regulated by the OSM/OSMR signaling, involved in the development of primary localized cutaneous amyloidosis. In Journal of dermatological science, 110, 53-60. doi:10.1016/j.jdermsci.2023.04.004. https://pubmed.ncbi.nlm.nih.gov/37100691/

5. Sharanek, Ahmad, Burban, Audrey, Laaper, Matthew, Soleimani, Vahab D, Jahani-Asl, Arezu. 2020. OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to ionizing radiation. In Nature communications, 11, 4116. doi:10.1038/s41467-020-17885-z. https://pubmed.ncbi.nlm.nih.gov/32807793/