Ikbkg-flox Mouse

Ikbkg, also known as IKBKG/NEMO (inhibitor of nuclear factor kappa B kinase regulatory subunit gamma), is essential for the NF-κB activation pathway [2,6]. The NF-κB pathway is involved in a variety of physiological and cellular processes, such as immunity, inflammation, cell proliferation, and survival [2].

Mutations in the Ikbkg gene are responsible for rare diseases like Anhidrotic Ectodermal Dysplasia with ImmunoDeficiency (EDA-ID) and Incontinentia Pigmenti (IP) [2]. In IP patients, Ikbkg mutations lead to a wide range of manifestations including skin, teeth, eyes, and central nervous system anomalies [3,4,5,7]. For instance, some IP patients have corpus callosum abnormalities which may be caused by Ikbkg mutations [3]. Additionally, in an atypical IP case, a novel germline missense mutation in Ikbkg led to persistent mucocutaneous hyperinflammation and immunodeficiency [8]. In colon cancer, RIPK2 promotes cancer progression by regulating BIRC3-mediated ubiquitination of Ikbkg, thus activating the NF-κB signaling pathway [9]. On the other hand, fluoride-induced down-regulation of Ikbkg gene expression inhibits hepatocytes senescence [1].

In conclusion, Ikbkg plays a crucial role in the NF-κB activation pathway, which is involved in multiple physiological processes. Its mutations are associated with rare genetic disorders like EDA-ID and IP, and it also has implications in conditions such as colon cancer and hepatocyte senescence. Research on Ikbkg using gene-based models helps to understand the molecular mechanisms underlying these diseases, potentially paving the way for new therapeutic strategies.