Age-specific regulation of clotting factor IX gene expression in normal and
transgenic mice
EJ Boland, YC Liu, CA Walter, DC Herbert, FJ Weaker, MW Odom and P Jagadeeswaran
Department of Cellular and Structural Biology, University of Texas Health
Science Center at San Antonio 78284-7762, USA.
Factor IX (FIX), a circulating serine protease that serves as an essential
component of the blood coagulation pathway, has been shown to increase with
age in humans. We show here that murine FIX mRNA and activity levels also
increase with age. Furthermore, one form of hemophilia B, hemophilia B
Leyden, which is caused by mutations within the promoter region of the FIX
gene, has a distinct age-dependent phenotype. To determine the source of
the age-related increases in FIX gene expression, we have analyzed the
regulation of the normal FIX gene promoter and FIX Leyden gene promoter
with the +13 mutation during aging by generating transgenic mice that
contain the -189 to +21 bp promoter segment ligated to a chloramphenicol
acetyltransferase reporter gene. We have established that the normal FIX
promoter and the Leyden promoter transgenes are expressed in a
tissue-specific manner in vivo. The normal FIX promoter transgene does not
show any differences in the pattern of expression with age or sex of the
organism, whereas the Leyden promoter transgene showed age-dependent
male-specific expression. This is the first demonstration of the FIX Leyden
phenotype in a transgenic mouse model.
Volume 86,
Issue 6,
pp. 2198-2205,
09/15/1995
Copyright © 1995 by The American Society of Hematology
