OVEREXPRESSION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN TRANSGENIC MICE IS CORRELATED WITH IMPAIRED LEARNING

Transgenic mice designated alphaMUPA over-produce in the brain murine urokinase-type plasminogen activator (uPA), an extracellular protease implicated in tissue remodeling. We have now localized, by in situ hyb ridization, extensive signal of uPA mRNA in the alphaMUPA cortex, hipp ocampus, and amygdala, sites that were not labeled in counterpart wild -type mice. Furthermore, biochemical measurements reveal a remarkably high level of enzymatic activity of uPA in the cortex and hippocampus of alphaMUPA compared with wild-type mice. We have used the alphaMUPA mice to examine whether the abnormal level of uPA in the cortex and th e limbic system affects learning ability. We report that alphaMUPA mic e perform poorly in tasks of spatial, olfactory, and taste-aversion le arning, while displaying normal sensory and motor capabilities. Our re sults suggest that uPA is involved in neural processes subserving a va riety of learning types.