标题：Investigation of age-related changes in LMNA splicing and expression of progerin in human skeletal muscles
作者：Luo, Yue-Bei; Mitrpant, Chalermchai; Johnsen, Russell D.; Fabian, Victoria A.; Fletcher, Sue; Mastaglia, Frank L.; Wilton, Steve D.
作者机构：[Luo, Yue-Bei; Mitrpant, Chalermchai; Johnsen, Russell D.; Fletcher, Sue; Mastaglia, Frank L.; Wilton, Steve D.] Australian Neuromuscular Res Inst, Ct 更多
通讯作者地址：[Wilton, SD]Murdoch Univ, Ctr Comparat Genom, 90 South St, Murdoch, WA 6150, Australia.
来源：INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
关键词：Human; mouse; skeletal muscle; lamin A/C; progerin; ageing
摘要：Age-related changes in splice-forms of LMNA, which encodes the nuclear lamina proteins lamin A/C, have not been investigated in skeletal muscle. In the rare premature ageing disease, Hutchinson-Gilford progeria syndrome (HGPS), de novo point mutations in LMNA activate a cryptic splice site in exon 11, resulting in a 150 base deletion in LMNA mRNA and accumulation of a truncated protein isoform, progerin. The LMN Delta 150 progerin transcript has also been found in trace quantities in tissues of healthy people and its implication in ` natural' ageing has been proposed. We therefore investigated the expression of progerin and lamin A/C in normal human and mouse skeletal muscles of different ages. LMN Delta 150 was detected in most muscle samples from healthy individuals aged 16-71 years, but was not present in any mouse muscle samples up to the age of 18 months. Real time qPCR of human muscle samples showed that there was an age-related increase in both the full length lamin A and LMN Delta 150 transcripts, whereas their protein levels did not change significantly with age. These findings indicate that there is a basal level of mis-splicing during LMNA expression that does not change with ageing in human muscle, but at levels that do not result in increased aberrant protein. The significance of these findings in the pathophysiology of muscle ageing is uncertain and warrants further investigation.