Key result
Heterozygous FBN1 mutant pigs exhibit human Marfan syndrome phenotypes including disrupted aortic elastic fibers.
Why the study?
Suitable animal models of Marfan syndrome are essential for understanding its pathogenesis and developing treatments, with pig models offering valuable physiological relevance to humans.
The generation of heterozygous FBN1 mutant cloned pigs provides a valuable large animal model that replicates key skeletal and cardiovascular phenotypes of human Marfan syndrome.
Establishes a large-animal Marfan model; leaves open translation to human therapies.
Marfan syndrome (MFS) is an autosomal dominant genetic disease caused by abnormal formation of the extracellular matrix with an incidence of 1 in 3, 000 to 5, 000. Patients with Marfan syndrome experience poor quality of life caused by skeletal disorders such as scoliosis, and they are at high risk of sudden death from cardiovascular impairment. Suitable animal models of MFS are essential for conquering this intractable disease. In particular, studies employing pig models will likely provide valuable information that can be extrapolated to humans because of the physiological and anatomical similarities between the two species. Here we describe the generation of heterozygous fibrillin-1 (FBN1) mutant cloned pigs (+/Glu433AsnfsX98) using genome editing and somatic cell nuclear transfer technologies. The FBN1 mutant pigs exhibited phenotypes resembling those of humans with MFS, such as scoliosis, pectus excavatum, delayed mineralization of the epiphysis and disrupted structure of elastic fibres of the aortic medial tissue. These findings indicate the value of FBN1 mutant pigs as a model for understanding the pathogenesis of MFS and for developing treatments.
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Umeyama et al. (2016) studied Marfan syndrome (animal model) (n=19). Heterozygous FBN1 mutation (+/Glu433AsnfsX98) vs. Wild-type pigs was evaluated on Phenotypic abnormalities resembling Marfan syndrome. Heterozygous FBN1 mutant cloned pigs exhibited phenotypes resembling human Marfan syndrome, including scoliosis, pectus excavatum, delayed bone mineralization, and disrupted aortic elastic fibres.