Age-specific regulation of clotting factor IX gene expression in normal and transgenic mice

E. J. Boland, Y. C. Liu, Christi A Walter, D. C. Herbert, F. J. Weaker, Michael W Odom, P. Jagadeeswaran

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2198-2205
Number of pages8
JournalBlood
Volume86
Issue number6
StatePublished - 1995

Fingerprint

Factor IX
Blood Coagulation Factors
Gene expression
Transgenic Mice
Gene Expression
Transgenes
Hemophilia B
Genes
Phenotype
Mutation
Chloramphenicol O-Acetyltransferase
Serine Proteases
Blood Coagulation
Reporter Genes
Genetic Promoter Regions
Coagulation
Blood
Demonstrations
Aging of materials
Messenger RNA

ASJC Scopus subject areas

  • Hematology

Cite this

Boland, E. J., Liu, Y. C., Walter, C. A., Herbert, D. C., Weaker, F. J., Odom, M. W., & Jagadeeswaran, P. (1995). Age-specific regulation of clotting factor IX gene expression in normal and transgenic mice. Blood, 86(6), 2198-2205.

Age-specific regulation of clotting factor IX gene expression in normal and transgenic mice. / Boland, E. J.; Liu, Y. C.; Walter, Christi A; Herbert, D. C.; Weaker, F. J.; Odom, Michael W; Jagadeeswaran, P.

In: Blood, Vol. 86, No. 6, 1995, p. 2198-2205.

Research output: Contribution to journalArticle

Boland, EJ, Liu, YC, Walter, CA, Herbert, DC, Weaker, FJ, Odom, MW & Jagadeeswaran, P 1995, 'Age-specific regulation of clotting factor IX gene expression in normal and transgenic mice', Blood, vol. 86, no. 6, pp. 2198-2205.
Boland EJ, Liu YC, Walter CA, Herbert DC, Weaker FJ, Odom MW et al. Age-specific regulation of clotting factor IX gene expression in normal and transgenic mice. Blood. 1995;86(6):2198-2205.
Boland, E. J. ; Liu, Y. C. ; Walter, Christi A ; Herbert, D. C. ; Weaker, F. J. ; Odom, Michael W ; Jagadeeswaran, P. / Age-specific regulation of clotting factor IX gene expression in normal and transgenic mice. In: Blood. 1995 ; Vol. 86, No. 6. pp. 2198-2205.
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AU - Odom, Michael W

AU - Jagadeeswaran, P.

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N2 - 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.

AB - 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.

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