A factor IX-deficient mouse model for hemophilia B gene therapy.
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.
Wang
L
L
Laboratory of Genetics, The Salk Institute, P.O. Box 85800, San Diego, CA 92186-5800, USA.
Zoppè
M
M
Hackeng
T M
TM
Griffin
J H
JH
Lee
K F
KF
Verma
I M
IM
D000256:Adenoviridae; D000818:Animals; D005091:Exons; D005164:Factor IX / Q000096:biosynthesis* / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D015698:Genomic Library; D002836:Hemophilia B / Q000235:genetics / Q000628:therapy*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011995:Recombination, Genetic
D005164:Factor IX