Evaluation of recombinant von Willebrand factor in a canine model of von Willebrand disease

Schwarz,; Dorner,; Mitterer,; Mundt,; Schlokat,; Pichler,; Turecek,

doi:10.1046/j.1365-2516.1998.0040s3053.x

Cited by 16 publications

(13 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The former are especially useful for pre-clinical study of human VWF concentrates. 80, 81 In the mild (type 1) VWD dogs, desmopressin can be used to discharge VWF from Weibel-Palade bodies in the endothelial cells. It has been shown in VWD dogs that IL-11 results in increased VWF message transcription and increased plasma levels of VWF.…”

Section: Von Willebrand Disease Animalsmentioning

confidence: 99%

Animal Models of Hemophilia and Related Bleeding Disorders

Lozier

Nichols

2013

Seminars in Hematology

View full text Add to dashboard Cite

Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study

show abstract

Section: Von Willebrand Disease Animalsmentioning

confidence: 99%

Animal Models of Hemophilia and Related Bleeding Disorders

Lozier

Nichols

2013

Seminars in Hematology

View full text Add to dashboard Cite

show abstract

“…In dogs, clinical signs of vWD are similar to those in humans (Schwarz et al. ), and include mucosal haemorrhage, prolonged bleeding following surgery and excessive bleeding with tooth eruption (Schwarz et al. ).…”

Section: Introductionmentioning

confidence: 96%

Evaluation of vonWillebrand Factor During Pregnancy, Lactation and Oestrous Cycle in Bitches Affected and Unaffected by vonWillebrand Disease

Mattoso

Takahira

Beier

et al. 2012

Reprod Domestic Animals

View full text Add to dashboard Cite

Plasmatic concentrations of von Willebrand Factor (vWF) increase during pregnancy in humans and dogs; however the mechanism of such increase is still not well defined. The aims of this study were: (i) to evaluate changes in vWF concentration during pregnancy and during the subsequent oestrous cycle in bitches affected and unaffected by von Willebrand Disease (vWD); (ii) to correlate the vWF levels and cortisol levels in both groups. Seven vWD affected (GI) and nine unaffected (GII) bitches were used. The animals were assessed during pregnancy, parturition, lactation and non-gestational oestrous cycle in 11 moments (Pregnancy 1, Pregnancy 2, Parturition, Lactation 1, Lactation 2, Lactation 3, Anestrus, Proestrus, Oestrus, Diestrus 1, and Diestrus 2). The following tests were performed; measurement of von Willebrand factor antigen (vWF:Ag), albumin and cortisol. In both groups, vWF concentration remained stable during the non-gestational oestrous cycle, but increased during pregnancy, with the highest value observed at parturition. Increases of 70% and 124% in vWF were seen in GI and GII, respectively, compared to anestrus. No correlation was found between vWF and cortisol. Values of vWF:Ag changed during pregnancy, with a peak at parturition, both in vWD affected and unaffected animals. Values of vWF were not altered in the different phases of the oestrous cycle following pregnancy in both groups. Evaluation of vWF during pregnancy can cause false negative results for vWD, but assessment can be performed at any point in the oestrous cycle of non-pregnant bitches.

show abstract

“…Likewise, infusion of human recombinant VWF into human subjects with severe VWD revealed a VWF:Ag half‐life of 21.9 hours, and a substantial stabilization of endogenous FVIII:C, peaking at 24 hours after infusion . In the canine model of severe VWD, infusion of human recombinant VWF resulted in a VWF:Ag half‐life of 21.6 hours in one dog and 22.1 hours in a second dog with sustained increases in endogenous FVIII levels . In our previous study, we showed that FVIII levels in mouse plasma could be restored up to 800 mU/mL when human recombinant VWF was infused into VWF (null) mice either by intravenous or intraperitoneal administration .…”

Section: Discussionmentioning

confidence: 84%

A rat model of severe VWD by elimination of the VWF gene using CRISPR/Cas9

Garcia

Flood

Haberichter

et al. 2020

Research and Practice in Thrombosis and Haemostasis

View full text Add to dashboard Cite

Background: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder, caused by quantitative and qualitative changes in von Willebrand factor (VWF). The biology of VWD, studied in canine, porcine, and murine models, differ in species-specific biology of VWF and the amenability to experimental manipulations such as phlebotomy. The factor VIII (FVIII) levels in these models are higher than in humans with type 3 VWD, suggesting functional differences between FVIII and VWF. ObjectivesTo develop a VWF knock out (VWF -/-) rat by excision of all 52 exons of the VWF locus. Methods:The entire VWF gene was eliminated in Sprague-Dawley (Crl:SD) rats via CRISPR/Cas9-mediated gene editing. VWF antigen (VWF:Ag), VWF propeptide, and VWF collagen IV binding (VWF:CB4) levels were determined by ELISA assays and FVIII chromogenic activity (FVIII:C) levels by chromogenic FVIII assays. Lateral tail veins were transected to measure bleeding time. VWF -/rats were infused with FVIII -/rat platelet poor plasma (PPP) to determine response of plasma FVIII. Results:Breeding of VWF ± rats yielded VWF -/offspring at normal Mendelian ratios. VWF:Ag, VWF propeptide, VWF:CB4, and FVIII:C plasma levels were undetectable in VWF -/rats. VWF -/rats bled longer and more than VWF +/and VWF +/+ rats when challenged. Transfusion of FVIII-deficient platelet-poor plasma induced a rapid rise in endogenous FVIII:C in VWF -/rats.Conclusion: This rat model of severe VWD due to elimination of the entire VWF gene recapitulates the severe secondary deficiency of FVIII seen in human type 3 VWD and facilitates the study of VWF and FVIII and their interactions. K E Y W O R D S CRISPR, factor VIII, rat model, severe von Willebrand disease, von Willebrand factor | 65 GARCIA et Al. Essentials• The biology of von Willebrand disease (VWD) has been studied in canine, porcine, and murine models.• We developed a rat model of severe VWD by CRISPR/Cas9 with total elimination of the von Willebrand factor (VWF) gene.• We found absent VWF antigen, VWF propeptide, VWF collagen 4 binding, factor VIII (FVIII) chromogenic activity, and increased bleeding when challenged.• This novel rat model facilitates the study of VWF and FVIII function and their interaction.

show abstract

Evaluation of recombinant von Willebrand factor in a canine model of von Willebrand disease

Cited by 16 publications

References 30 publications

Animal Models of Hemophilia and Related Bleeding Disorders

Animal Models of Hemophilia and Related Bleeding Disorders

Evaluation of vonWillebrand Factor During Pregnancy, Lactation and Oestrous Cycle in Bitches Affected and Unaffected by vonWillebrand Disease

A rat model of severe VWD by elimination of the VWF gene using CRISPR/Cas9

Contact Info

Product

Resources

About