Human ADAMTS13 was recently identified as a gene encoding von Willebrand factor-cleaving protease, hADAMTS13. Both congenital and acquired defects in this enzyme can cause thrombotic thrombocytopenic purpura. hADAMTS13 consists of 1,427 amino acid residues and is composed of multiple structural domains including thrombospondin type 1 motifs and CUB domains. To analyze the functional roles of these domains in vivo, we determined the cDNA sequence of the mouse ortholog, mADAMTS13. Unexpectedly, two forms of the mouse Adamts13 gene were isolated that differed in the insertion of an intracisternal A particle (IAP) retrotransposon including a premature stop codon. The IAP insertion was found in BALB/c, C3H/He, C57BL/6, and DBA/2 strains but not in the 129/Sv strain. The outbred ICR strain had either the IAP-free or IAP-inserted allele or both. IAP-free Adamts13 encoded mADAMTS13L, a protein of 1,426 amino acid residues with the same domain organization as hADAMTS13. In contrast, IAP-inserted Adamts13 encoded a C-terminally truncated enzyme, mADAMTS13S, that is comprised of only 1,037 amino acid residues and lacking the C-terminal two thrombospondin type 1 motifs and two CUB domains. Strain specificity was also confirmed by reverse transcription-PCR and Northern blot analyses. Both recombinant mADAMTS13L and mADAMTS13S exhibited von Willebrand factor cleaving activities in vitro. The natural variation in mouse ADAMTS13 should allow for the determination of hitherto unknown functions of its C-terminal domains in vivo.