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

Autor: Joonyoung R. Kim, Paul H. Kim, Ashley Presnell, Yiping Tu, Stephen G. Young
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Nucleus, Vol 14, Iss 1 (2023)
Druh dokumentu: article
ISSN: 19491034
1949-1042
1949-1034
DOI: 10.1080/19491034.2023.2262308
Popis: ABSTRACTThe Lmna knockout mouse (Lmna–/–) created by Sullivan and coworkers in 1999 has been widely used to examine lamin A/C function. The knockout allele contains a deletion of Lmna 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 Lmna cDNA containing exon 1–7 + exon 12 sequences. Because exon 12 encodes prelamin A’s CaaX motif, the mutant lamin A is assumed to be farnesylated. In the current study, we found that the truncated lamin A in Lmna–/– 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 Lmna transcripts in Lmna–/– 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 Lmna–/– 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 Lmna–/– MEFs and adds to our understanding of a commonly used strain of Lmna–/– mice.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje