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Publication : Neonatal bleeding in transgenic mice expressing urokinase-type plasminogen activator.

First Author  Heckel JL Year  1990
Journal  Cell Volume  62
Issue  3 Pages  447-56
PubMed ID  1696178 Mgi Jnum  J:135419
Mgi Id  MGI:3793574 Doi  10.1016/0092-8674(90)90010-c
Citation  Heckel JL, et al. (1990) Neonatal bleeding in transgenic mice expressing urokinase-type plasminogen activator. Cell 62(3):447-56
abstractText  Spontaneous intestinal and intra-abdominal bleeding was observed in a high percentage of newborn transgenic mice carrying the murine urokinase-type plasminogen activator (uPA) gene linked to the albumin enhancer/promoter. These hemorrhagic events were directly related to transgene expression in the liver and the development of high plasma uPA levels. Two lines were established from surviving founder mice that displayed multigenerational transmission of the bleeding phenotype. Fatal hemorrhaging developed between 3 and 84 hr after birth in about half of the transgenic offspring of these lines; transgenic pups that did not bleed nevertheless passed the phenotype to their young. The phenotypic variability could not be explained by differences in transgene expression. All transgenic neonates were severely hypofibrinogenemic and displayed loss of clotting function that extended beyond the risk period for bleeding. These mice provide a means of studying the pathophysiology of plasminogen hyperactivation and evaluating therapeutic protocols designed to prevent bleeding.
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