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

•TGF beta2 heterozygosity synergizes with fibrillin1 hypomorphism to cause early death in mice.•Death is not from dissection and rupture.•Mortality is associated with abnormal aortic valves. To assess the contribution of individual TGF-β isoforms to aortopathy in Marfan syndrome (MFS), we quantified...

Full description

Saved in:

Bibliographic Details
Published in:	Matrix biology Vol. 121; pp. 41 - 55
Main Authors:	Sachan, Nalani, Phoon, Colin K.L., Zilberberg, Lior, Kugler, Matthias C., Ene, Taylor, Mintz, Shana B., Murtada, Sae-Il, Weiss, Dar, Fishman, Glenn I., Humphrey, Jay D., Rifkin, Daniel B.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-08-2023
Subjects:	Animals Aorta Aortic regurgitation Aortic valves Biomechanical evaluation Fibrillin-1 - genetics Haploinsufficiency Marfan syndrome Marfan Syndrome - genetics Mice Phenotype TGF-β2 Thoracic aortic aneurysms Transforming Growth Factor beta2 - genetics Thoracic aortic aneurysms Aortic valves Biomechanical evaluation Latent TGF-β Binding Proteins Thoracic Aortic Aneurysm TGF-β2 Aortic regurgitation Marfan syndrome
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	•TGF beta2 heterozygosity synergizes with fibrillin1 hypomorphism to cause early death in mice.•Death is not from dissection and rupture.•Mortality is associated with abnormal aortic valves. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 NS, LZ, CKLP, MCK, SM, GIF, JH, and DBR collected and analyzed the data. NS, JH, and DBR wrote the manuscript. JH and DBR acquired funding. All authors read and revised the paper. Current address: Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90,048, USA. Author contributions
ISSN:	0945-053X 1569-1802
DOI:	10.1016/j.matbio.2023.05.004