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von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene.

Publication ,  Journal Article
Nichols, WC; Cooney, KA; Mohlke, KL; Ballew, JD; Yang, A; Bruck, ME; Reddington, M; Novak, EK; Swank, RT; Ginsburg, D
Published in: Blood
June 1, 1994

An animal model for human type I von Willebrand disease (vWD) has been previously described in the inbred mouse strain RIIIS/J. Murine vWD is characterized by a prolonged bleeding time, normal von Willebrand factor (vWF) multimer distribution, autosomal dominant inheritance, and proportionately decreased plasma vWF antigen, ristocetin cofactor, and factor VIII (FVIII) activities. To study the molecular genetics of murine vWD, a portion of the vWF gene surrounding exon 28 was cloned, sequenced, and used to develop two informative DNA sequence polymorphisms for rapid genotyping by DNA polymerase chain reaction. RIIIS/J mice were crossed with PWK/Ph mice, an inbred line of Mus musculus musculus, and the F1 progeny backcrossed to the parental PWK/Ph strain. vWF antigen levels in F1 mice were not significantly different from the parental RIIIS/J strain but were markedly decreased compared with the parental PWK/Ph mice. Genetic linkage analysis of 104 backcross progeny showed no correlation between vWF antigen level and vWF genotype. These data indicate that murine vWD is caused by a defect at a novel genetic locus, distinct from the murine vWF gene. The distribution of vWF antigen levels among backcross progeny suggests the presence of one major dominant vWD gene in the RIIIS/J mouse with possible modifying contributions from one or more additional minor loci. These observations may provide new insights into the molecular basis and variable expressivity of human vWD.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

June 1, 1994

Volume

83

Issue

11

Start / End Page

3225 / 3231

Location

United States

Related Subject Headings

  • von Willebrand Factor
  • von Willebrand Diseases
  • Molecular Sequence Data
  • Mice, Inbred BALB C
  • Mice
  • Immunology
  • Enzyme-Linked Immunosorbent Assay
  • Disease Models, Animal
  • Base Sequence
  • Animals
 

Citation

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Nichols, W. C., Cooney, K. A., Mohlke, K. L., Ballew, J. D., Yang, A., Bruck, M. E., … Ginsburg, D. (1994). von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene. Blood, 83(11), 3225–3231.
Nichols, W. C., K. A. Cooney, K. L. Mohlke, J. D. Ballew, A. Yang, M. E. Bruck, M. Reddington, E. K. Novak, R. T. Swank, and D. Ginsburg. “von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene.Blood 83, no. 11 (June 1, 1994): 3225–31.
Nichols WC, Cooney KA, Mohlke KL, Ballew JD, Yang A, Bruck ME, et al. von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene. Blood. 1994 Jun 1;83(11):3225–31.
Nichols, W. C., et al. “von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene.Blood, vol. 83, no. 11, June 1994, pp. 3225–31.
Nichols WC, Cooney KA, Mohlke KL, Ballew JD, Yang A, Bruck ME, Reddington M, Novak EK, Swank RT, Ginsburg D. von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene. Blood. 1994 Jun 1;83(11):3225–3231.

Published In

Blood

ISSN

0006-4971

Publication Date

June 1, 1994

Volume

83

Issue

11

Start / End Page

3225 / 3231

Location

United States

Related Subject Headings

  • von Willebrand Factor
  • von Willebrand Diseases
  • Molecular Sequence Data
  • Mice, Inbred BALB C
  • Mice
  • Immunology
  • Enzyme-Linked Immunosorbent Assay
  • Disease Models, Animal
  • Base Sequence
  • Animals