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Mice lacking proSAAS display alterations in emotion, consummatory behavior and circadian entrainment
Dipendra K Aryal1, Ramona M Rodriguiz1,2, Ngoc Lien Nguyen1
1Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA.
Genes, Brain, and Behavior
|July 25, 2022
Summary
ProSAAS-derived peptides are crucial for regulating anxiety-like behaviors, emotional responses, and circadian clock function in mice. Knockout mice lacking these peptides exhibit significant behavioral and physiological alterations.
Area of Science:
- Neuroendocrinology
- Behavioral Neuroscience
- Metabolic Research
Background:
- ProSAAS is a neuroendocrine protein processed into peptides like bigLEN and PEN.
- These peptides activate GPR171 and GPR83 receptors, respectively.
- Previous research linked proSAAS peptides to body weight, circadian rhythms, and anxiety.
Purpose of the Study:
- To investigate the role of proSAAS-derived peptides in mouse behavior and physiology.
- To characterize the behavioral and metabolic phenotypes of proSAAS knockout mice.
Main Methods:
- Generation and analysis of proSAAS knockout mice.
- Behavioral testing including open field, light-dark emergence, elevated zero maze, and fear conditioning.
- Metabolic monitoring including water/food consumption, urine production, and respiratory exchange ratio.
- Circadian rhythm assessment under various light conditions.
Main Results:
- ProSAAS knockout mice exhibited increased anxiety-like behaviors and impaired fear responses.
- Mutant mice showed reduced water consumption and urine production.
- An elevated respiratory exchange ratio indicated decreased fat metabolism during the light phase.
- ProSAAS knockout mice failed to shift their circadian clock in response to light pulses.
Conclusions:
- ProSAAS-derived peptides play a significant role in modulating emotional behaviors, water balance, and circadian clock regulation.
- These findings highlight the broad physiological impact of proSAAS peptide signaling.

