Table 3.

Genotype-phenotype traits of mouse strains as it pertains to VWF and ADAMTS-13.

Strain	Traits	Advantages	Disadvantages
C57BL/6	•Insertion of IAP retrotransposon including premature stop codon, resulting in expression of truncated ADAMTS-13 (lacks distal 2 TSP1 repeats and CUB domains) [179] •Moderate-high plasma VWF levels with normal clearance [180]	•Most common inbred strain with extensive genetic tools, knockout libraries, and well-characterized background, suitable for gene targeting studies •Useful to study the role of distal ADAMTS-13 domains •VWF levels provide comparable baseline to humans	•ADAMTS-13 protein does not recapitulate human ADAMTS-13 structure, limiting translational value (activity is ∼10-fold lower) [55,179] •Pure C57BL/6 mice are resistant to spontaneous TTP [99] •Higher tail-clip bleeding assay variability than other strains [181]
129/Sv	•No IAP retrotransposon, expresses ADAMTS-13 with similar domain organization as humans [182] •Moderate plasma VWF levels with normal clearance [180]	•Full-length ADAMTS-13 expression makes this strain ideal for the study of ADAMTS-13 biology •Commonly used for embryonic stem cell-derived gene targeting, making it a natural strain for many knockout models	•Pure 129/Sv mice are resistant to spontaneous TTP [99] •Less extensive reagent and tool availability than C57BL/6 strain
CASA/Rk	•ADAMTS-13 structure and biology not well characterized •Extremely high VWF levels, 10-fold higher than C57BL/6 strain (Mvwf2, Mvwf3, Mvwf4 alleles) [183,184]	•Commonly introduced to C57BL/6 and 129/Sv lines to facilitate development of TTP [99] •High VWF phenotype facilitates study of VWF modifier genetics, synthesis, and QTL mapping [184] •Mvwf3 and Mvwf4 show conservation of synteny with human chromosomal segments, suggesting translational relevance [184]	•Poorly characterized ADAMTS-13 biology •Wild-derived strain (Mus musculus castaneus) with limited genetic tools, reagents, and characterized background •Numerous interacting QTLs create complex genetic architecture •Breeding and colony maintenance may be more challenging
CAST/Ei	•VWF/ADAMTS-13 biology least characterized •VWF levels presumed higher but not explicitly measured [127]	•Can be introduced to C57BL/6 and 129/Sv lines to facilitate development of TTP [99] •High VWF phenotype may be useful for study of VWF modifier genetics, synthesis, and QTL mapping	•Wild-derived strain (Mus musculus castaneus) with limited genetic tools, reagents, and characterized background •Largely uncharacterized strain in context of VWF

ADAMTS-13, a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13; CUB, complement C1r/C1s, Uegf, Bmp1; IAP, intracisternal A-type particle; QTL, quantitative trait locus; TSP1, thrombospondin type-1 repeats; TTP, thrombotic thrombocytopenic purpura; VWF, von Willebrand factor.