Treatment of a Hemophilia B Mouse Model with Platelet-Targeted Expression of Factor IX Padua

Li, Binbin; Wu, Zhihan; Xu, Wenjue; Han, Wenwen; Liu, Jiayu; Wang, Dawei; Zhang, Guowei

doi:10.1089/hum.2020.309

Cited by 2 publications

(9 citation statements)

References 37 publications

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“…We followed the guidelines of the Animal Research: Reporting of In Vivo Experiments (ARRIVE). FIX inhibitors in 2bFXa-HB mice were developed through intraperitoneal injection of recombinant human FIX (BeneFIX, Pfizer, China) as previously described 16 . Briefly, 200 U/kg recombinant hFIX mixed with Freund’s adjuvant (SigmaAldrich, China) was injected into the mice twice with an interval of 3 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…Blood samples were counted using an animal blood counter (Mindray, China). Plasma, platelets and platelet lysates were prepared as previously described 16 . Three mixtures of platelet agonists were used for platelet activation.…”

Section: Methodsmentioning

confidence: 99%

“…FIX inhibitors in mouse plasma were determined with the modified Bethesda assay as previously described 16 . An FIX activity assay kit (HYPHEN BioMed, France) was used to measure FIX activity following the manufacturer’s instruction.…”

Section: Methodsmentioning

confidence: 99%

“…The tail bleeding assay was designed based on previous work 16 . The mouse was placed on a warm pad after anesthetized by 2.5% avertin.…”

Section: Methodsmentioning

confidence: 99%

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Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets

Han,

Huang,

et al. 2023

Sci Rep

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Platelet-stored activated blood coagulation factor X (FXa) has great potential in the gene therapy of hemophilia B (HB). However, we still need to understand more about the properties of FXa-storing platelets and how dietary factors affect them. We created transgenic mice called 2bFXa-HB, which had stable expression and storage of FXa in their platelets, resulting in the alleviation of the bleeding disorder in these mice. Even after inducing anti-factor IX (FIX) inhibitors in 2bFXa-HB mice, the hemorrhage phenotype could still be rescued by the expression of FXa. The activation capacity of 2bFXa-HB platelets remained unchanged, and there were no signs of elevated thrombotic risk in these mice. In an acute alcohol exposure mouse model, a single administration of alcohol reduced both the number of platelets and their activation capacity, as well as impaired coagulation function. However, it did not increase the markers of thrombotic risk in either 2bFXa-HB or HB mice. These results suggest that FXa storage in platelets is safe and effective for treatment of HB, but alcohol could impair the therapeutic effect of FXa-containing platelets.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The tail bleeding assay was designed based on previous work 16 . The mouse was placed on a warm pad after anesthetized by 2.5% avertin.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets

Han,

Huang,

et al. 2023

Sci Rep

Self Cite

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“…Mice have long been the preferred species for biomedical research aimed at generating human models for congenital conditions ( 1 , 2 ), particularly congenital coagulopathies ( 3 ). Murine models have been designed for hemophilia A (factor VIII deficiency) ( 4 ) and for hemophilia B (factor IX deficiency) ( 5 ). Factor V (FV) deficient animal models have been created for mice as well as for zebra fish, but the individuals born at full term died a few days later due to breakthrough bleeds or because they were subjected to different procedures ( 6 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

Standardization of Coagulation Factor V Reference Intervals, Prothrombin Time, and Activated Partial Thromboplastin Time in Mice for Use in Factor V Deficiency Pathological Models

2022

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Factor V together with activated factor X forms the prothrombinase complex, which transforms prothrombin into thrombin. The Mus musculus species is characterized by very high levels of this factor and short clotting times, which hinders accurate measurements. For that reason, a detailed characterization of such parameters is indispensable. A method was designed as part of this study to provide an accurate determination and standardization of factor V levels, prothrombin time and activated partial thromboplastin time in Mus musculus. Those parameters were evaluated in a sample of 66 healthy animals using a semi-automated coagulometer and human diagnostic reagents in an attempt to determine the most appropriate time of day for the extractions. A mouse-based protocol was designed, capable of making corrections to the samples at dilutions of 1:100 for factor V and at of 1:3 for prothrombin time. The goal was to smoothen the calibration curves, which often present with steep slopes and narrow measurement ranges between one calibration point and another. It was found that the most stable period for blood sample extraction was that comprised between the first 6 h of light. No clinical differences were observed between the sexes and reference intervals were established for factor V (95.80% ± 18.14; 25.21 s ± 1.34), prothrombin time (104.31% ± 14.52; 16.85 s ± 1.32) and activated partial thromboplastin time (32.86 s ± 3.01). The results obtained are applicable to human or veterinary biomedical research, to transfusional medicine or to pathological models for diseases such as factor V deficiency.

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Treatment of a Hemophilia B Mouse Model with Platelet-Targeted Expression of Factor IX Padua

Cited by 2 publications

References 37 publications

Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets

Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets

Standardization of Coagulation Factor V Reference Intervals, Prothrombin Time, and Activated Partial Thromboplastin Time in Mice for Use in Factor V Deficiency Pathological Models

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