Morphometric analysis of thoracic aorta in Slc39a13/Zip13-KO mice
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Ehlers–Danlos syndrome (EDS) is a collection of inheritable diseases involving the musculoskeletal, integumentary and visual systems. Spondylodysplastic EDS-ZIP13 (spEDS-ZIP13: OMIM 612350) was recently defined as a new form of EDS. Although vasculitis has been found in many spEDS-ZIP13 patients, vascular pathology has not been included as a pathognomonic lesion of this type of EDS. We investigate the morphometry of the thoracic aorta in wild-type and Zip13-knockout (Zip13-KO) mice. Our assessment found abnormalities in the number and morphology of elastic and cellular components in the aortic wall, especially the tunica media, of Zip13-KO mice, indicating aortic fragility. Accordingly, our major findings (vascular smooth muscle cells with small nuclei, small percentage of elastic membrane area per tunica media, many large elastic flaps) should be considered vulnerable characteristics indicating fragility of the aorta in patients with spEDS-ZIP13.
KeywordsAorta Elasticity Elastic membrane Morphometry Slc39a13/Zip13-KO mouse
The authors express sincere gratitude to Drs. Hiromi Ueda and Jun Minaguchi of the Laboratory of Anatomy, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan, for their technical advice.
This work was partially supported by The Maple Foundation.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
- Deren-Wagemann I, Kuliszkiewicz-Janus M, Schiller J (2010) The ehlers-danlos syndrome. Adv Exp Med Biol 19:537–542Google Scholar
- Fukada T, Civic N, Furuichi T, Shimoda S, Mishima K, Higashiyama H, Idaira Y, Asada Y, Kitamura H, Yamasaki S, Hojyo S, Nakayama M, Ohara O, Koseki H, Dos Santos HG, Bonafe L, Ha-Vinh R, Zankl A, Unger S, Kraenzlin ME, Beckmann JS, Saito I, Rivolta C, Ikegawa S, Superti-Furga A, Hirano T (2008) The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-β signaling pathways. PLoS One 3:e3642CrossRefGoogle Scholar
- Giunta C, Elçioglu NH, Albrecht B, Eich G, Chambaz C, Janecke AR, Yeowell H, Weis M, Eyre DR, Kraenzlin M, Steinmann B (2008) Spondylocheiro dysplastic form of the Ehlers-Danlos syndrome--an autosomal-recessive entity caused by mutations in the zinc transporter gene SLC39A13. Am J Hum Genet 82:1290–1305CrossRefGoogle Scholar
- Malfait F, Francomand C, Byers P, Belmont J, Berglund B, Black J, Bloom L, Bowen JM, Brady AF, Burrows NP, Castori M, Cohen H, Colombi M, Demirdas S, De Backer J, De Paepe A, Fournel-Gigleux S, Frank M, Ghali N, Giunta C, Grahame R, Hakim A, Jeunemaitre X, Johnson D, Juul-Kristensen B, Kapferer-Seebacher I, Kazkaz H, Kosho T, Lavallee ME, Levy H, Mendoza-Londono R, Pepin M, Pope FM, Reinstein E, Robert L, Rohrbach M, Sanders L, Sobey GJ, Van Damme T, Vandersteen A, Van Mourik C, Voermans N, Wheeldon N, Zschocke J, Tinkle B (2017) The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet 175C:8–26CrossRefGoogle Scholar
- Rosenbloom J, Abrams WR, Mecham R (1993) Extracellular matrix 4: the elastic fiber. FASEB J (13):1208–1218Google Scholar
- Rurali E, Perrucci GL, Pilato CA, Pini A, Gaetano R, Nigro P, Pompilio G (2018) Precise therapy for thoracic aortic aneurysm in marfan syndrome: a puzzle nearing its solution. Prog Cardiovasc Dis. https://doi.org/10.1016/j.pcad.2018.07.020