Il6ra, also known as Interleukin 6 receptor subunit alpha, encodes the alpha subunit of the interleukin-6 receptor. IL-6 is a pleiotropic cytokine with broad effects on immune and non-immune cells, and Il6ra is crucial for IL-6 signaling. The IL-6/Il6ra signaling pathway is involved in multiple biological processes, including inflammation, cell growth, and differentiation [1].

In a Müller-glial-cell-specific Il6ra knockout mouse model, loss of IL-6 cis-signaling in Müller glial cells led to accelerated retinal functional decline and thinning of the inner nuclear layer in diabetic mice, indicating the role of Il6ra in maintaining retinal structure and function in diabetes [2]. In another study, suppression of Il6ra specifically in area postrema neurons using CRISPR/dCas9 interference attenuated cancer cachectic phenotypes and hyperactivity in the associated neural network in male mice, suggesting its role in cancer cachexia [3].

In conclusion, Il6ra is essential for IL-6 signaling, playing a role in various biological processes. The use of gene knockout mouse models, such as the Müller-glial-cell-specific Il6ra knockout and the Il6ra-suppressed area postrema neuron model, has revealed its significance in diseases like diabetic retinopathy and cancer cachexia, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Hunter, Christopher A, Jones, Simon A. . IL-6 as a keystone cytokine in health and disease. In Nature immunology, 16, 448-57. doi:10.1038/ni.3153. https://pubmed.ncbi.nlm.nih.gov/25898198/

2. Glass, Joshua, Robinson, Rebekah L, Greenway, Grace, Jones, Garrett, Sharma, Shruti. . Diabetic Müller-Glial-Cell-Specific Il6ra Knockout Mice Exhibit Accelerated Retinal Functional Decline and Thinning of the Inner Nuclear Layer. In Investigative ophthalmology & visual science, 64, 1. doi:10.1167/iovs.64.15.1. https://pubmed.ncbi.nlm.nih.gov/38038619/

3. Sun, Qingtao, van de Lisdonk, Daniëlle, Ferrer, Miriam, Janowitz, Tobias, Li, Bo. 2024. Area postrema neurons mediate interleukin-6 function in cancer cachexia. In Nature communications, 15, 4682. doi:10.1038/s41467-024-48971-1. https://pubmed.ncbi.nlm.nih.gov/38824130/