Key result
Heterozygous TGF-β2 loss causes ~80% early mortality in Marfan mice via cardiopulmonary defects.
Why the study?
The contribution of individual TGF-β isoforms to aortopathy in Marfan syndrome was unclear.
p-value: p=0.0001
TGF-β2 loss exacerbates non-aortic defects in Marfan mice; leaves open isoform-specific targeting in patients pending human data.
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.
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Sachan et al. (2023) studied Marfan syndrome (MFS). TGF-β2 heterozygous null mutation vs. Fbn1 mgR/mgR (MFS only) mice was evaluated on Mortality by postnatal day 20 (p=0.0001). Heterozygous loss of TGF-β2 in Marfan syndrome mice caused 80% mortality by postnatal day 20 (p=0.0001) associated with cardiac and pulmonary defects rather than aortic rupture.
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