Growth and behavioral development in plasminogen gene-targeted mice.

The plasminogen system, in addition to its major role in fibrinolyis, is believed to play a key role in development of the nervous system. The purpose of this study was to directly examine and quantify the importance of plasminogen in physical and behavioral development in plasminogen deficient mice (Plg-/-), plasminogen heterozygous mice (Plg+/-), and wild-type mice (Plg+/+, WT) at 2-21 days of age. Remarkably, little difference in growth and behavioral development was observed between Plg-/- and WT mice. Body weight gain and the milestones of physical development-ear detachment, eye opening and teeth eruption were similar from 2-21 days of age. Differences were found in physical development only after 4 wks of age, body weight gain was less and vaginal patency was delayed in the Plg-/- mice compared to WT mice. Behaviors, assessed during the 2-21 days of age period, developed in the Plg-/- mice in a pattern similar to WT mice. Specifically, no differences were found between Plg-/- and WT mice in the development of reflexes, neuromotor ability, motor coordination, locomotor activity, reaction to gravitational positioning, integration of motor and vestibular systems, olfactory development, and incidence of audiogenic seizure susceptibility. However, Plg-/- mice demonstrated a faster surface righting response and a faster latency for audiogenic seizure susceptibility, as well as an increase in the number of grooming bouts at age 17-21 days. These differences indicate that a plasminogen deficiency alters reactivity and the response to stress. The weight of the pituitary was smaller and pituitary and plasma corticotrophin releasing hormone were elevated in the Plg-/- mice compared to the WT mice. The results of this study suggest a role for the plasminogen system in hormone processing and neuroendocrine regulation.