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Growth and behavioral development in plasminogen gene-targeted mice
J Hoover-Plow1, N Wang, V Ploplis
1Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44196, USA. hooverj@ccf.org
Summary
Plasminogen deficiency minimally impacts early mouse development but alters stress responses and neuroendocrine regulation later in life, affecting hormone processing and pituitary function.
Area of Science:
- Neuroscience
- Developmental Biology
- Biochemistry
Background:
- The plasminogen system is crucial for fibrinolysis and is implicated in nervous system development.
- Understanding plasminogen's role in neurodevelopment is essential for identifying potential therapeutic targets.
Purpose of the Study:
- To quantify the impact of plasminogen deficiency on physical and behavioral development in mice.
- To investigate the role of plasminogen in neuroendocrine regulation and stress response.
Main Methods:
- Comparative analysis of plasminogen-deficient (Plg-/-), heterozygous (Plg+/-), and wild-type (Plg+/+) mice from 2-21 days of age.
- Assessment of physical development milestones (e.g., ear detachment, eye opening, weight gain) and behavioral development (e.g., reflexes, motor coordination, seizure susceptibility).
- Evaluation of pituitary weight and corticotrophin-releasing hormone levels.
Main Results:
- No significant differences in early growth or physical development (2-21 days) between Plg-/- and WT mice.
- Delayed vaginal patency and reduced weight gain observed in Plg-/- mice after 4 weeks.
- Plg-/- mice showed altered stress responses, including faster righting reflex, faster audiogenic seizure latency, increased grooming, smaller pituitary weight, and elevated corticotrophin-releasing hormone.
Conclusions:
- Plasminogen deficiency has a limited effect on early physical and behavioral development but significantly impacts later-life stress reactivity and neuroendocrine function.
- The plasminogen system plays a role in hormone processing and neuroendocrine regulation.
- Further research is warranted to elucidate the precise mechanisms linking plasminogen to neuroendocrine pathways.