The effects of intrinsic pathway protease deficiencies on plasminogen-deficient mice.
Plasminogen (Plg)-deficient mice experience wasting and have decreased longevity due to disseminated fibrin deposition. We generated mice with combined deficiencies of Plg and coagulation factor IX (fIX) or XI (fXI) to determine the effects on the Plg null phenotype. Mice lacking Plg and fIX (Plg(-/-)/fIX-/-) have lower mortality at age 6 months than Plg(-/-)/fIX+/+ mice (15% and 67%, respectively) and less severe wasting, consistent with the importance of fIX in fibrin formation. In contrast, combined Plg and fXI deficiency (Plg(-/-)/fXI-/-) reduces life span (more than 90% mortality at 6 months) and is associated with leukocyte infiltration of the lungs and pulmonary fibrosis. These abnormalities are not seen in Plg-/- or Plg(-/-)/fIX-/- animals. Activated fXI is thought to function primarily as a fIX activator; however, our observation suggests that fXI may have functions in regulation of inflammation or tissue repair distinct from its role in coagulation.
Hematology/Oncology Division, Department of Pathology, Vanderbilt University, 777 MRB II, 2220 Pierce Ave, Nashville, TN 37232-6307, USA.
Qiufang
Q
Cheng
Yong
Y
Zhao
William E
WE
Lawson
Vasiliy V
VV
Polosukhin
Joyce E
JE
Johnson
Timothy S
TS
Blackwell
David
D
Gailani
D000818:Animals; D005164:Factor IX / Q000235:genetics / Q000378:metabolism*; D005172:Factor XI / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation; D008136:Longevity; D008168:Lung / Q000002:abnormalities / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010447:Peptide Hydrolases / Q000172:deficiency* / Q000378:metabolism; D010958:Plasminogen / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D011658:Pulmonary Fibrosis
D005164:Factor IX; D010958:Plasminogen; D005172:Factor XI; D010447:Peptide Hydrolases