In:
Disease Models & Mechanisms, The Company of Biologists
Abstract:
Variable clinical differences have been observed between the FBN1 gene mutation and the classical Marfan phenotype in humans. Although FBN1 knockout (KO), or dominant negative mutant mice are widely used as an animal model for MFS, these mice cannot recapitulate the genotype/phenotype relationship of Marfanoid-progeroid-lipodystrophy syndrome (MPL), a syndrome caused by a mutation in the C-terminus of fibrillin-1, the penultimate exon of the FBN1 gene. Here we describe the generation of a rabbit MPL model with C-terminal truncation of fibrillin-1 using a CRISPR/Cas9 system. FBN1 Heterozygous (FBN1 Het) rabbits faithfully recapitulated the phenotypes of MFS, including muscle wasting and impaired connective tissue, ocular syndrome and aortic dilation. Moreover, skin symptoms, lipodystrophy, growth retardation and dysglycemia were also seen in these FBN1 Het rabbits, which have not been reported in other animal models. In conclusion, this novel rabbit model mimics the histopathological changes and functional defects of MPL syndrome, and may become a valuable model for studies of pathogenesis and drug screening for MPL syndrome.
Type of Medium:
Online Resource
ISSN:
1754-8411
,
1754-8403
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2018
detail.hit.zdb_id:
2451104-3
Permalink