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Int J Clin Exp Pathol 2013;6(12):2778-2786

Original Article
Investigation of age-related changes in LMNA splicing and expression of progerin in
human skeletal muscles

Yue-Bei Luo, Chalermchai Mitrpant, Russell D Johnsen, Victoria A Fabian, Sue Fletcher, Frank L Mastaglia, Steve D Wilton

Centre for Neuromuscular and Neurological Disorders, Australian Neuro-Muscular Research Institute, Perth, Australia; Laboratory of
Neuromuscular Disorders, Department of Neurology, Qilu Hospital, Shandong University, Jinan, China; Department of Biochemistry, Faculty of
Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Section of Neuropathology, Department of Anatomical Pathology, Royal Perth
Hospital, Perth, Australia; Centre for Comparative Genomics, Murdoch University, Perth, Australia; Institute for Immunology and Infectious
Diseases, Murdoch University, Perth, Australia

Received September 19, 2013; Accepted October 26, 2013; Epub November 15, 2013; Published December 1, 2013

Abstract: 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 LMNA ∆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. LMNA ∆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 LMNA ∆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. (IJCEP1309051).

Keywords: Human, mouse, skeletal muscle, lamin A/C, progerin, ageing

Address correspondence to: Dr. Steve D Wilton, Centre for Comparative Genomics, Murdoch University, 90 South Street, Murdoch, Western
Australia, Australia, 6150. Tel: + 61 8 9360 2305; Fax: + 61 8 93607238; E-mail: swilton@ccg.murdoch.edu.au