Revisiting the truncated lamin A produced by a commonly used strain of knockout mice.

The knockout mouse () created by Sullivan and coworkers in 1999 has been widely used to examine lamin A/C function. The knockout allele contains a deletion of 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 cDNA containing exon 1-7 + exon 12 sequences. Because exon 12 encodes prelamin A's motif, the mutant lamin A is assumed to be farnesylated. In the current study, we found that the truncated lamin A in 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 transcripts in 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 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 MEFs and adds to our understanding of a commonly used strain of mice.