• ADAM metallopeptidase with thrombospondin type 1 motif 13 (ADAMTS13) is the primary processing enzyme for von Willebrand factor (VWF), regulated by a feedback loop involving ultra-large VWF multimers. Typically, endothelial-derived ultra-large VWF promotes platelet aggregation under high shear stress, while ADAMTS13 cleaves it into smaller, less thrombogenic forms. Deficiency or inhibition of ADAMTS13—a key driver of thrombotic thrombocytopenic purpura (TTP)—leads to uncontrolled platelet microthrombi and multiorgan ischemia.
• Gene editing strategy: The exons 1-23 of mouse Adamts13 gene are replaced by human whole ADAMTS13 genomic sequence including promoter, 5'UTR, 3'UTR and coding region in B-hADAMTS13 mice. The human ADAMTS13 expression is driven by human ADAMTS13 promoter, while mouse Adamts13 gene transcription and translation will be disrupted.
• mRNA Expression Analysis: Mouse Adamts13 mRNA was detectable in wild-type C57BL/6JNifdc mice. Human ADAMTS13 mRNA was detectable only in homozygous B-hADAMTS13 mice but not in wild-type mice.
• Application: This product is used for pharmacodynamics and safety evaluation of Type 1 von Willebrand disease (VWD), myocardial infarction, stroke, cerebral malaria, and preeclampsia

Gene editing strategy for B-hADAMTS13 mice.

• The exons 1-23 of mouse Adamts13 gene are replaced by human whole ADAMTS13 genomic sequence including promoter, 5'UTR, 3'UTR and coding region in B-hADAMTS13 mice. The human ADAMTS13 expression is driven by human ADAMTS13 promoter, while mouse Adamts13 gene transcription and translation will be disrupted.

Strain specific analysis of ADAMTS13 mRNA expression in wild-type C57BL/6JNifdc mice and homozygous humanized B-hADAMTS13 mice by RT-PCR. Liver RNA were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hADAMTS13 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human ADAMTS13 primers. Human ADAMTS13 mRNA was detectable only in homozygous B-h ADAMTS13 mice but not in wild-type C57BL/6JNifdc mice. Mouse Adamts13 mRNA was detectable only in wild-type mice. Human sequences were confirmed via Sanger Sequencing.

Strain specific ADAMTS13 expression analysis in homozygous B-hADAMTS13 mice by ELISA. Plasma were collected from wild-type mice C57BL/6JNifdc mice (+/+) (n=3, male, 8-week-old; n=3, female, 8-week-old) and homozygous B-hADAMTS13 mice (H/H) (n=3, male, 8-week-old; n=3, female, 8-week-old), and analyzed by ELISA with strain-specific ADAMTS13 ELISA kit (Human ADAMTS13 ELISA Kit, abcam ab234559). Human ADAMTS13 was exclusively detectable in homozygous humanized B-hADAMTS13 mice but not in wild-type mice. Values are expressed as mean ± SEM.