Adamts10-KO Mouse

ADAMTS10, a secreted metalloproteinase, is crucial for extracellular matrix (ECM) turnover and tissue development. It binds to fibrillin microfibrils, promoting their formation and influencing fibrillin isoform composition. It also plays a role in regulating the bioavailability of TGF-β superfamily growth factors, which are involved in multiple biological processes [1,2,3,4,5]. Genetic models, such as mouse models, have been valuable in studying ADAMTS10's functions.

In Adamts10 -/- mice, ocular microfibrils persist due to reduced fibrillin-2 cleavage, highlighting ADAMTS10's role in clearing ocular fibrillin-2 [2]. In a mouse model with a glaucoma-causative mutation of ADAMTS10 (ADAMTS10G661R/G661R), there is RGC dysfunction, optic nerve axon structural changes, increased apoptosis in the retina during postnatal development, and decreased TGFβ signaling, suggesting ADAMTS10's role in regulating TGFβ signaling [4].

In conclusion, ADAMTS10 is essential for ECM-related functions, especially in microfibril biogenesis and TGFβ signaling regulation. Mouse models, including gene-knockout and mutation-carrying models, have significantly contributed to understanding its role in diseases like glaucoma and Weill-Marchesani syndrome, providing insights into disease mechanisms and potential therapeutic targets.