Sex-specific role for the long noncoding RNA Pnky in mouse behavior

• Published in: bioRxiv
• Main Authors: Saha, Parna, Andersen, Rebecca E, Hong, Sung Jun, Gil, Eugene, Simms, Jeffrey, Lim, Daniel A
• Format: Journal Article Paper
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 07.12.2023
• Subjects: Acoustic startle response; Affective disorders; Animal behavior; Artificial chromosomes; Bacterial artificial chromosomes; Cognitive ability; Emotional behavior; Mental disorders; Non-coding RNA; Phenotypes; Startle response; Transgenes
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2023.12.05.569777

The human brain expresses thousands of different long noncoding RNAs (lncRNAs), and aberrant expression of specific lncRNAs has been associated with cognitive and psychiatric disorders. While a growing number of lncRNAs are now known to regulate neural cell development and function, relatively few have been shown to underlie animal behavior, particularly with genetic strategies that establish lncRNA function in . is an evolutionarily conserved, neural lncRNA that regulates brain development. Using mouse genetic strategies, we show that has sex-specific roles in mouse behavior and that this lncRNA underlies specific behavior by functioning in . Male -knockout (KO) mice have deficits in cued fear recall, a type of Pavlovian associative memory. In female -KO mice, the acoustic startle response (ASR) is increased and accompanied by a decrease in prepulse inhibition (PPI), both of which are behaviors altered in affective disorders. Remarkably, expression of from a bacterial artificial chromosome (BAC) transgene reverses the ASR phenotype of female -KO mice, demonstrating that underlies specific animal behavior by functioning in . More broadly, these data provide genetic evidence that a lncRNA gene and its function in can play a key role in the behavior of adult mammals, contributing fundamental knowledge to our growing understanding of the association between specific lncRNAs and disorders of cognition and mood.