Physiological roles of long noncoding RNAs: insight from knockout mice

•lncRNAs exert important cellular functions with diverse regulatory mechanisms.•Different targeting strategies yield different insights about the lncRNA locus.•Genetic ablation of lncRNAs reveals their important functions in vivo.

Long noncoding RNAs (lncRNAs) are a pervasive and recently recognized class of genes. lncRNAs have been proposed to modulate gene expression and nuclear architecture, but their physiological functions are still largely unclear. Several recent efforts to inactivate lncRNA genes in mouse models have shed light on their functions. Different genetic strategies have yielded specific lessons about the roles of lncRNA transcription, the lncRNA transcript itself, and underlying sequence elements. Current results indicate important functions for lncRNAs in organ development, immunity, organismal viability, and in human diseases.