A Factor IX-Deficient Mouse Model for Hemophilia B Gene Therapy

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 21; pp. 11563 - 11566
• Main Authors: Wang, Lili, Zoppe, Monica, Hackeng, Tilman M., Griffin, John H., Lee, Kuo-Fen, Verma, Inder M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 14-10-1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Adenoviridae; Animal models; Animals; Biological Sciences; Blood plasma; Complementary DNA; Exons; Factor IX - biosynthesis; Factor IX - genetics; Female; Gene therapy; Gene Transfer Techniques; Genes; Genetic Therapy; Genetic Vectors; Genomic Library; Hemophilia; Hemophilia B; Hemophilia B - genetics; Hemophilia B - therapy; Heterozygote; Homozygote; Humans; Male; Medical research; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Partial thromboplastin time; Recombination, Genetic; Rodents; Sex chromosomes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.21.11563

We have generated a mouse where the clotting factor IX (FIX) gene has been disrupted by homologous recombination. The FIX nullizygous (-/-) mouse was devoid of factor IX antigen in plasma. Consistent with the bleeding disorder, the factor IX coagulant activities for wild-type (+/+), heterozygous (+/-), and homozygous (-/-) mice were 92%, 53%, and <5%, respectively, in activated partial thromboplastin time assays. Plasma factor IX activity in the deficient mice (-/-) was restored by introducing wild-type murine FIX gene via adenoviral vectors. Thus, these factor IX-deficient mice provide a useful animal model for gene therapy studies of hemophilia B.