TGFβ-2 haploinsufficiency causes early death in mice with Marfan syndrome.

Autor: Sachan N; Department of Cell Biology, NYU Grossman School of Medicine, New York, NY, 10016, USA. Electronic address: nalani.sachan@nyumc.org., Phoon CKL; Department of Pediatrics, NYU Grossman School of Medicine, New York, NY, 10016, USA., Zilberberg L; Department of Cell Biology, NYU Grossman School of Medicine, New York, NY, 10016, USA., Kugler MC; Department of Medicine, NYU Grossman School of Medicine, New York, NY, 10016, USA., Ene T; Department of Cell Biology, NYU Grossman School of Medicine, New York, NY, 10016, USA., Mintz SB; Department of Medicine, NYU Grossman School of Medicine, New York, NY, 10016, USA., Murtada SI; Department of Biomedical Engineering, Yale University, New Haven, CT, 06520, USA., Weiss D; Department of Biomedical Engineering, Yale University, New Haven, CT, 06520, USA., Fishman GI; Department of Medicine, NYU Grossman School of Medicine, New York, NY, 10016, USA., Humphrey JD; Department of Biomedical Engineering, Yale University, New Haven, CT, 06520, USA., Rifkin DB; Department of Cell Biology, NYU Grossman School of Medicine, New York, NY, 10016, USA; Department of Medicine, NYU Grossman School of Medicine, New York, NY, 10016, USA.
Jazyk: angličtina
Zdroj: Matrix biology : journal of the International Society for Matrix Biology [Matrix Biol] 2023 Aug; Vol. 121, pp. 41-55. Date of Electronic Publication: 2023 May 20.
DOI: 10.1016/j.matbio.2023.05.004
Abstrakt: To assess the contribution of individual TGF-β isoforms to aortopathy in Marfan syndrome (MFS), we quantified the survival and phenotypes of mice with a combined fibrillin1 (the gene defective in MFS) hypomorphic mutation and a TGF-β1, 2, or 3 heterozygous null mutation. The loss of TGF-β2, and only TGF-β2, resulted in 80% of the double mutant animals dying earlier, by postnatal day 20, than MFS only mice. Death was not from thoracic aortic rupture, as observed in MFS mice, but was associated with hyperplastic aortic valve leaflets, aortic regurgitation, enlarged aortic root, increased heart weight, and impaired lung alveolar septation. Thus, there appears to be a relationship between loss of fibrillin1 and TGF-β2 in the postnatal development of the heart, aorta and lungs.
Competing Interests: Declaration of Competing Interest All of the authors declare no conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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