TGF β-2 Haploinsufficiency Causes Early Death in Mice with Marfan Syndrome

Matrix Biol. 2023 May 20:S0945-053X(23)00061-6. doi: 10.1016/j.matbio.2023.05.004. Online ahead of print.ABSTRACTTo 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 post-natal 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 post-natal development of the heart, aorta and lungs.PMID:37217119 | DOI:10.1016/j.matbio.2023.05.004
Source: Matrix Biology - Category: Molecular Biology Authors: Source Type: research