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Functional deficits in PAK5, PAK6 and PAK5/PAK6 knockout mice
Melody A Furnari1, Michelle L Jobes, Tanya Nekrasova
1Joint Program in Toxicology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America.
Plos One
|April 18, 2013
Summary
Group II p21-activated kinases (PAKs) are crucial for neuronal development. Pak5/Pak6 double knockout mice show significant deficits in locomotion and learning, indicating their vital roles.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- p21-activated kinases (PAKs) are key effectors of Rho-family GTPases.
- Group II PAKs (PAK4, PAK5, PAK6) are implicated in neurite outgrowth, filopodia formation, and cell survival.
- Pak4 knockout mice are embryonic lethal, while Pak5 and Pak6 knockout models are viable.
Purpose of the Study:
- To investigate the distinct behavioral phenotypes of Pak5 and Pak6 knockout mice compared to wild-type.
- To further characterize the impact of combined Pak5 and Pak6 knockout on mouse behavior.
Main Methods:
- Generation and comparison of Pak5 knockout, Pak6 knockout, and Pak5/Pak6 double knockout mice.
- Behavioral assessments including locomotor activity, rotorod test, resident intruder paradigm, and active avoidance assay.
Main Results:
- Pak6 knockout mice exhibited increased body weight.
- Pak5/Pak6 double knockout mice displayed reduced activity and poorer performance in rotorod and active avoidance tests.
- All knockout genotypes showed decreased aggression in the resident intruder paradigm.
Conclusions:
- While single Pak5 or Pak6 knockout mice show some behavioral alterations, the combined Pak5/Pak6 knockout results in the most pronounced deficits in locomotion and learning/memory.
- These findings highlight the critical and potentially synergistic roles of PAK5 and PAK6 in regulating complex behaviors.
