Il6st-flox Mouse

Il6st, also known as interleukin 6 cytokine family signal transducer or gp130, is a key component of the receptor complex for the IL-6 family of cytokines, including IL-6, IL-11, LIF, etc. These cytokines activate various intracellular signalling pathways such as JAK/STAT, MAPK and PI3K, which are essential for immune homeostasis, haematopoiesis, inflammation, development and metabolism [2,3].

Mutations in Il6st can lead to various diseases. Dominant-negative mutations in human Il6st underlie autosomal dominant hyper-IgE syndrome (AD-HIES), with patients suffering from cold staphylococcal lesions, mucocutaneous candidiasis, severe allergy, and skeletal abnormalities [5,6]. A mosaic Il6st variant inducing constitutive GP130 cytokine receptor signalling causes neonatal onset immunodeficiency with autoinflammation and dysmorphy [7]. In hepatocellular carcinoma, impaired degradation of IL6ST by chaperone-mediated autophagy promotes cell proliferation and migration [1]. In Parkinson's disease, IL6ST is involved in the α-Synuclein-induced neuroinflammation injury through the IL6ST-AS/STAT3/HIF-1α axis [4].

In conclusion, Il6st is crucial for the normal function of the IL-6 cytokine family signalling pathways. Studies on Il6st-related mouse models (implied by the human disease-causing mutations) could potentially help understand its role in diseases like AD-HIES, neonatal immunodeficiency, hepatocellular carcinoma, and Parkinson's disease, providing insights for diagnosis and treatment strategies.