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RTL1/PEG11 , which has been associated with anxiety disorders, is a retrotransposon-derived imprinted gene in the placenta. However, imprinting patterns and functions of RTL1 in the brain have not been well-investigated. We found  Rtl1  was paternally, but not maternally, expressed in brain stem, thalamus, and hypothalamus of mice, and imprinting status of  RTL1  was maintained in human brain. Paternal  Rtl1  knockout ( Rtl1 m+/p-  ) mice had higher neonatal death rates due to impaired suckling, and low body weights beginning on embryonic day 16.5. High paternal expression of  Rtl1  was detected in the locus coeruleus (LC) and  Rtl1 m+/p-   mice showed an increased delay in time of onset for action potentials and inward currents with decreased neuronal excitability of LC neurons. Importantly,  Rtl1 m+/p-   mice exhibited behaviors associated with anxiety, depression, fear-related learning and memory, social dominance, and low locomotor activity. Taken together, our findings demonstrate RTL1 is imprinted in brain, mediates emotional and social behaviors, and regulates excitability in LC neurons.

RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus