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October 4, 2018Blood AdvancesOpen Access

The H1HA mouse strain demonstrated ristocetin-induced platelet aggregation similar to human platelet-rich plasma, which was inhibited by monoclonal antibody NMC-4; NMC-4 also inhibited FeCl3-induced mouse carotid artery thrombosis.

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Population

Mouse models including wild-type, VWFh28 knockin, human GPIbα transgenic, and double humanized strains.

Comparison

Generation of a double humanized mouse strain… vs Wild-type mice and single humanized strains.

Design

Preclinical

Authors

SKSachiko KanajiJOJennifer N. OrjeTKTaisuke Kanaji

Discussion

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Overview

New VWF knockin mouse enables GPIbα-targeted antithrombotic testing; leaves open human translation.

Structured PICO

P
Population
Mouse models including wild-type (M1MA), VWFh28 knockin (M1HA), human GPIbα transgenic (H1MA), and double humanized (H1HA) strains.
I
Intervention
Generation of a double humanized mouse strain (H1HA) with humanized GPIbα-VWFA1 binding, and testing with monoclonal antibody NMC-4.
C
Comparator
Wild-type mice (M1MA) and single humanized strains (M1HA, H1MA).
O
Outcome
Tail bleeding time, thrombogenesis after carotid artery injury, and ristocetin-induced platelet aggregation.surrogate

The development of the H1HA mouse strain provides a fully humanized in vivo model for studying platelet GPIbα-VWFA1 interactions and testing novel antithrombotic therapies.

Cite This Study

Kanaji et al. (2018) studied this question.

synapsesocial.com/papers/6a968dcb33d7b00ae7bb86e1https://doi.org/10.1182/bloodadvances.2018023507
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