Neonatal bleeding in transgenic mice expressing urokinase-type plasminogen activator

Cell. 1990 Aug 10;62(3):447-56. doi: 10.1016/0092-8674(90)90010-c.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Northern
  • Fibrinogen / analysis
  • Gastrointestinal Hemorrhage / genetics*
  • Gene Expression
  • Growth Hormone / genetics*
  • Humans
  • Liver / enzymology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Oligonucleotide Probes
  • Phenotype
  • Plasminogen Activators / genetics*
  • Platelet Count
  • Protein Precursors / genetics*
  • RNA / genetics
  • RNA / isolation & purification
  • RNA, Messenger / genetics
  • Restriction Mapping
  • Urokinase-Type Plasminogen Activator / genetics*


  • Oligonucleotide Probes
  • Protein Precursors
  • RNA, Messenger
  • RNA
  • Fibrinogen
  • Growth Hormone
  • Plasminogen Activators
  • Urokinase-Type Plasminogen Activator