The functions of long noncoding RNAs (lncRNAs) have mainly been studied using 
cultured cell lines, and this approach has revealed the involvement of lncRNAs 
in a variety of biological processes, including the epigenetic control of gene 
expression, post-transcriptional regulation of mRNA, and cellular proliferation 
and differentiation. Recently, increasing numbers of studies have investigated 
the functions of lncRNAs using gene-targeted model mice, largely confirming the 
physiological importance of lncRNA-mediated regulation in individual animals. In 
some cases, however, the results obtained by studies using knockout mice have 
been somewhat inconsistent with those of the preceding cell-based analyses. In 
this review, I will summarize the lessons that we are learning from the 
reverse-genetic studies of lncRNAs, namely the importance of noncoding DNA 
elements, the weak correlation between expression level and phenotypic 
prominence, the existence of tissue- and condition-specific phenotypes and 
incomplete penetrance, and the function of lncRNAs as precursor molecules. This 
article is part of a Special Issue entitled: Clues to long noncoding RNA 
taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.