Skin Disease in Laminopathy-Associated Premature Aging Tomás McKenna, Agustín Sola Carvajal, Maria Eriksson  Journal of Investigative Dermatology  Volume 135, Issue 11, Pages 2577-2583 (November 2015) DOI: 10.1038/jid.2015.295 Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Impaired lamin A/C in segmental progeroid syndromes. (a) A list of selected LMNA mutations causing atypical Werner syndrome (AWS), Hutchinson–Gilford progeria syndrome (HGPS), and atypical progeroid syndrome (APS). Exons 1–9 and a section of 10 encode lamin C (lamin C–specific amino acids in green). Lamin A results from alternative splicing using exons 1–12, without the lamin C–specific part of exon 10. Conserved α-helical regions of the central rod domain are labeled coil 1/1B/2A+2B. Underlying numbers refer to primary sequence locations. NLS, nuclear localization signal. (b) Prelamin A maturation in wild type, HGPS (and several APS), and restrictive dermopathy (RD). (c) Skin fibroblast nuclei, blue (DNA), young/unaffected, aged/unaffected, and HGPS, far right shows the HGPS nuclei in red (progerin). Journal of Investigative Dermatology 2015 135, 2577-2583DOI: (10.1038/jid.2015.295) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Histopathology of progerin expression. (a) Disease severity increases with higher levels of progerin. (b–d and f–h) K5 (green), DNA (blue). (b and f) Mouse lamin (La) A/C (red) is expressed by E17.5. (c and g) Epidermal progerin expression (red), wild-type (c) and progeroid (g) E17.5. Progerin expression follows K5 expression (g). (d and h) Adult wild-type (d), progeroid (h) mouse skin, progerin (red) showing epidermal hyperplasia and hyperparakeratosis (h). (e and i) Hematoxylin and eosin (H&E) staining of wild-type (e) and progeroid (i) mouse skin. (j and k) Impaired wound healing. A 3 mm wound site from wild-type (j) and progeroid (k) mice 7 days after wounding. K5 (blue), dividing cells (red). Disorganized wound edges, delayed reepithelialization, and (inset) increased cell proliferation at wound edges in k. Dashed lines indicate wound centers. Scale bars (b–i)=20 μm, (j and k)=200 μm. Journal of Investigative Dermatology 2015 135, 2577-2583DOI: (10.1038/jid.2015.295) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions