Revisiting the truncated lamin A produced by a commonly used strain of <i>Lmna</i> knockout mice

The <i>Lmna</i> knockout mouse (<i>Lmna</i>^–/–) created by Sullivan and coworkers in 1999 has been widely used to examine lamin A/C function. The knockout allele contains a deletion of <i>Lmna</i> intron 7–exon 11 sequences and was reported to be a null allele. Later, Jahn and coworkers discovered that the mutant allele produces a 54-kDa truncated lamin A and identified, by RT-PCR, a <i>Lmna</i> cDNA containing exon 1–7 + exon 12 sequences. Because exon 12 encodes prelamin A’s <i>CaaX</i> motif, the mutant lamin A is assumed to be farnesylated. In the current study, we found that the truncated lamin A in <i>Lmna</i>^–/– mouse embryonic fibroblasts (MEFs) was predominantly nucleoplasmic rather than at the nuclear rim, leading us to hypothesize that it was not farnesylated. Our study revealed that the most abundant <i>Lmna</i> transcripts in <i>Lmna</i>^–/– MEFs contain exon 1–7 but not exon 12 sequences. Exon 1–7 + exon 12 transcripts were detectable by PCR but in trace amounts. We suspect that these findings explain the nucleoplasmic distribution of the truncated lamin A in <i>Lmna</i>^–/– MEFs, and subsequent cell transduction experiments support this suspicion. A truncated lamin A containing exon 1–7 sequence was nucleoplasmic, whereas a lamin A containing exon 1–7 + exon 12 sequences was located along the nuclear rim. Our study explains the nucleoplasmic targeting of truncated lamin A in <i>Lmna</i>^–/– MEFs and adds to our understanding of a commonly used strain of <i>Lmna</i>^–/– mice.