huINHBE-6xHIS Mouse

Inhibin βE subunit (INHBE) is a member of the transforming growth factor-β (TGF-β) superfamily and is highly specifically expressed in hepatocytes. The INHBE precursor protein is proteolytically processed to generate the mature inhibin βE subunit, which is involved in various biological processes, including cell proliferation, apoptosis, immune regulation, and hormone secretion. During obesity- and diabetes-associated metabolic disorders, INHBE expression is altered and participates in the regulation of lipid metabolism, adipose storage, and insulin sensitivity. Studies have shown that hepatic INHBE expression is positively correlated with insulin resistance and body mass index (BMI) in humans, suggesting that INHBE may function as a hepatokine involved in systemic metabolic regulation under obesity-associated insulin-resistant conditions ^[1]. In 2022, studies from Alnylam Pharmaceuticals and the Regeneron Genetics Center (RGC) revealed a close relationship between INHBE and adipose regulation. Research demonstrated that rare loss-of-function (LOF) variants in INHBE may promote healthier adipose storage patterns, improve metabolic profiles, and reduce the risk of obesity-associated inflammation, dyslipidemia, and type 2 diabetes mellitus (T2D). Patients carrying such variants exhibited improved fat distribution, reduced abdominal adiposity, better metabolic health, and significantly decreased risks of cardiovascular disease and T2D ^[2-4]. These findings indicate that INHBE is a liver-specific negative regulator of adipose storage. Suppression of INHBE expression may represent a potential therapeutic strategy for metabolic disorders associated with abnormal fat distribution and storage. Therefore, several small nucleic acid pharmaceutical companies, including Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, and Wave Life Sciences, are currently developing RNA interference (RNAi)-based therapeutics targeting INHBE for the treatment of obesity and related metabolic diseases ^[5-7].

huINHBE-6xHIS mice were generated based on the huINHBE humanized model (Catalog No.: C001533). In this model, the genomic region from the start codon to the 3’UTR of mouse Inhbe was replaced with the corresponding region of human INHBE, and a 6xHIS tag sequence was inserted upstream of the stop codon in exon 2 of the human INHBE gene. This modification enables specific detection of human INHBE protein using His-tag antibodies. The huINHBE-6xHIS mouse model is suitable for investigating the mechanisms of obesity and metabolic diseases, developing therapeutics targeting human INHBE, studying liver-adipose tissue crosstalk, and exploring the pathogenesis of type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD).