Adamo, Christin S. ORCID: 0000-0002-8560-6153, Beyens, Aude, Schiavinato, Alvise, Keene, Douglas R., Tufa, Sara F., Morgelin, Matthias, Brinckmann, Jurgen, Sasaki, Takako, Niehoff, Anja, Dreiner, Maren, Pottie, Lore, Muino-Mosquera, Laura, Gulec, Elif Yilmaz, Gezdirici, Alper ORCID: 0000-0002-2432-9279, Braghetta, Paola, Bonaldo, Paolo, Wagener, Raimund, Paulsson, Mats, Bornaun, Helen, De Rycke, Riet, De Bruyne, Michiel, Baeke, Femke, Devine, Walter P., Gangaram, Balram, Tam, Allison ORCID: 0000-0001-6940-9240, Balasubramanian, Meena ORCID: 0000-0003-1488-3695, Ellard, Sian, Moore, Sandra, Symoens, Sofie, Shen, Joseph, Cole, Stacey, Schwarze, Ulrike, Holmes, Kathryn W., Hayflick, Susan J., Wiszniewski, Wojciech, Nampoothiri, Sheela, Davis, Elaine C., Sakai, Lynn Y., Sengle, Gerhard and Callewaert, Bert (2022). EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis. Am. J. Hum. Genet., 109 (12). S. 2230 - 2254. CAMBRIDGE: CELL PRESS. ISSN 1537-6605

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Abstract

EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the inter-face between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elasto-genesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1-or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Adamo, Christin S.UNSPECIFIEDorcid.org/0000-0002-8560-6153UNSPECIFIED
Beyens, AudeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schiavinato, AlviseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keene, Douglas R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tufa, Sara F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morgelin, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brinckmann, JurgenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sasaki, TakakoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niehoff, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dreiner, MarenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pottie, LoreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muino-Mosquera, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gulec, Elif YilmazUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gezdirici, AlperUNSPECIFIEDorcid.org/0000-0002-2432-9279UNSPECIFIED
Braghetta, PaolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bonaldo, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagener, RaimundUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paulsson, MatsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bornaun, HelenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Rycke, RietUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Bruyne, MichielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baeke, FemkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Devine, Walter P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gangaram, BalramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tam, AllisonUNSPECIFIEDorcid.org/0000-0001-6940-9240UNSPECIFIED
Balasubramanian, MeenaUNSPECIFIEDorcid.org/0000-0003-1488-3695UNSPECIFIED
Ellard, SianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moore, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Symoens, SofieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shen, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cole, StaceyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarze, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holmes, Kathryn W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hayflick, Susan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiszniewski, WojciechUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nampoothiri, SheelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davis, Elaine C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sakai, Lynn Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sengle, GerhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Callewaert, BertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-697360
DOI: 10.1016/j.ajhg.2022.10.010
Journal or Publication Title: Am. J. Hum. Genet.
Volume: 109
Number: 12
Page Range: S. 2230 - 2254
Date: 2022
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1537-6605
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OLIGOMERIC MATRIX PROTEIN; CUTIS LAXA; LYSYL OXIDASE; ELASTIC FIBERS; FIBULIN-4; FIBRILLIN; MATURATION; BONE; GENE; THROMBOSPONDIN-5Multiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69736

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