德晋贵宾厅

• ADAMTS1, a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, a class of zinc-ion dependent, secreted metalloproteinases that contain the type I thrombospondin motif (TSP) and exhibit a disintegrin-like structure. The ADAMTS1 protein plays a dual role in tumorigenesis: it can either promote or inhibit tumor growth.
• The ADAMTS1 protein plays important roles in extracellular matrix remodeling, angiogenesis, and inflammation. It participates in vascular remodeling and is associated with diseases such as atherosclerosis and hypertension. Modulating ADAMTS1 activity may help stabilize atherosclerotic plaques or reduce vascular inflammation, offering potential therapeutic strategies for patients with cardiovascular diseases.
• Targeting strategy: The exons 1-9 of mouse Adamts1 gene that encode the whole molecule (ATG to STOP codon), including 3’UTR were replaced by human counterparts in B-hADAMTS1 mice. The promoter and 5’UTR region of the mouse gene are also retained. The human ADAMTS1 expression is driven by endogenous mouse Adamts1 promoter, while mouse Adamts1 gene transcription and translation will be disrupted.
• Application: This humanized mouse model is utilized for evaluating the efficacy and toxicity of monoclonal antibody biologics in cancer, cardiovascular, and inflammatory diseases.

Gene targeting strategy for B-hADAMTS1 mice. The exons 1-9 of mouse Adamts1 gene that encode the whole molecule (ATG to STOP codon), including 3’UTR were replaced by human counterparts in B-hADAMTS1 mice. The promoter and 5’UTR region of the mouse gene are also retained. The human ADAMTS1 expression is driven by endogenous mouse Adamts1 promoter, while mouse Adamts1 gene transcription and translation will be disrupted.

Strain specific analysis of ADAMTS1 mRNA expression in wild-type C57BL/6N mice and B-hADAMTS1 mice by RT-PCR. Lung RNA was isolated from wild-type C57BL/6N mice (+/+) and homozygous B-hADAMTS1 mice (H/H), and then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human ADAMTS1 primers. Mouse Adamts1 mRNA was detectable only in wild-type C57BL/6N mice. Human ADAMTS1 mRNA was detectable only in homozygous B-hADAMTS1 mice but not in wild-type mice.

Western blot analysis of ADAMTS1 protein expression in homozygous B-hADAMTS1 mice. Various tissue lysates were collected from wild-type C57BL/6N mice (+/+) and homozygous B-hADAMTS1 mice (H/H), and then analyzed by western blot with anti-human ADAMTS1 antibody (CST, 12897T). 40 μg total proteins were loaded for western blotting analysis. ADAMTS1 was detected in the heart, spleen, lung, kidney, skeletal muscle and brain of homozygous B-hADAMTS1 mice.