huANGPTL7 Mouse

The ANGPTL7 gene encodes a secreted protein within the angiopoietin-like family, distinguished by its N-terminal coiled-coil domain and C-terminal fibrinogen-like domain. This protein is instrumental in extracellular matrix formation and organization, and functions as a negative regulator of angiogenesis, essential for maintaining corneal avascularity ^[1]. ANGPTL7 expression is highly prominent in the corneal stroma and ocular trabecular meshwork, the latter being critical for intraocular pressure (IOP) regulation. Its presence is also noted in adipose, neural, uterine, and hematopoietic stem/progenitor cells, where it influences lipid metabolism, inflammation, and hematopoiesis. Dysregulation of ANGPTL7 is significantly implicated in several pathologies, most notably glaucoma, type 2 diabetes mellitus (T2DM), and obstructive sleep apnea (OSA) ^[1-3]. In glaucoma, elevated ANGPTL7 in the trabecular meshwork enhances extracellular matrix deposition, increasing aqueous humor outflow resistance and consequently IOP ^[1]. For T2DM, ANGPTL7 contributes to insulin resistance through SOCS3 upregulation, leading to IRS1 degradation and compromised insulin signaling, thereby impairing glucose uptake ^[2]. In OSA, elevated ANGPTL7 levels correlate with disease severity, suggesting a role in the associated inflammatory, oxidative stress, and potential vascular remodeling processes ^[3].

The huANGPTL7 mouse is a humanized model, constructed by replacing the sequences from 5'UTR to 3'UTR of the endogenous mouse Angptl7 gene with the corresponding human ANGPTL7 gene sequence. huANGPTL7 mice can be used for research into the pathogenesis of glaucoma, type 2 diabetes mellitus (T2DM), and obstructive sleep apnea (OSA). They are also useful for the screening, development, and safety evaluation of ANGPTL7-targeted drugs.