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

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Aberrant expression of long noncoding RNAs (lncRNAs) is linked to cognitive and psychiatric disorders.
• While lncRNAs regulate neural development, few are known to underlie animal behavior.
• Pnky is an evolutionarily conserved neural lncRNA crucial for brain development.

Purpose of the Study:

• To investigate the role of the neural lncRNA Pnky in mouse behavior.
• To determine if Pnky has sex-specific functions in behavior.
• To explore the mechanism by which Pnky influences behavior, including its potential to function in trans.

Main Methods:

• Utilized mouse genetic strategies, including knockout models.
• Assessed associative fear learning and memory in male Pnky-knockout mice.
• Evaluated the acoustic startle response in female Pnky-knockout mice and rescue experiments using a bacterial artificial chromosome transgene.

Main Results:

• Male Pnky-knockout mice exhibited decreased context generalization in fear learning.
• Female Pnky-knockout mice showed an increased acoustic startle response.
• Transgenic Pnky expression in female knockouts rescued the acoustic startle response phenotype, indicating Pnky functions in trans.

Conclusions:

• Pnky plays sex-specific roles in mouse behavior, affecting fear learning and startle response.
• This lncRNA can modulate specific animal behaviors by functioning in trans.
• These findings highlight the potential of specific lncRNAs to underlie cognitive and mood disorders.