Enhanced blood coagulation and fibrinolysis in mice lacking histidine-rich glycoprotein (HRG).
Histidine-rich glycoprotein (HRG) is a serum protein belonging to the cystatin superfamily. HRG may play a regulatory role in hemostasis and innate immunity. However, this role is uncertain because of a lack of rigorous testing in an animal model. We generated mice lacking the translation start point of exon 1 of the Hrg gene, effectively resulting in a null mutation (Hrg-/-). The mice were viable and fertile but had no HRG in their blood. Antithrombin activity in the plasma of Hrg-/- mice was higher than in the plasma of heterozygous Hrg+/- or wild-type Hrg+/+ mice. The prothrombin time was shorter in Hrg-/- mice than in Hrg+/- and Hrg+/+ mice. Bleeding time after tail tip amputation in Hrg-/- mice was shorter than in Hrg+/+ mice. The spontaneous fibrinolytic activity in clotted blood of Hrg-/- mice was higher than in Hrg+/+ mice. These findings suggest that HRG plays a role as both an anticoagulant and an antifibrinolytic modifier, and may regulate platelet function in vivo.
Tsuchida-Straeten
N
N
IZKF BIOMAT, University Hospital, RWTH Aachen, Pauwelsstrasse 30, D-52074, Aachen, Germany.
Ensslen
S
S
Schäfer
C
C
Wöltje
M
M
Denecke
B
B
Moser
M
M
Gräber
S
S
Wakabayashi
S
S
Koide
T
T
Jahnen-Dechent
W
W
D000818:Animals; D001760:Bleeding Time; D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology; D015139:Blotting, Southern; D003001:Cloning, Molecular; D005091:Exons; D005342:Fibrinolysis; D005822:Genetic Vectors; D005838:Genotype; D006579:Heterozygote; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D012867:Skin / Q000378:metabolism; D013234:Stem Cells; D014945:Wound Healing; D000099053:Histidine-Rich Glycoprotein
D011506:Proteins; D000099053:Histidine-Rich Glycoprotein