Generation of heterozygous fibrillin-1 mutant cloned pigs from genome-edited foetal fibroblasts

Kazuhiro Umeyama, Koota Watanabe, Masahito Watanabe, Keisuke Horiuchi, Kazuaki Nakano, Masateru Kitashiro, Hitomi Matsunari, Tokuhiro Kimura, Yoshimi Arima, Oltea Sampetrean, Masaki Nagaya, Masahiro Saito, Hideyuki Saya, Kenjiro Kosaki, Hiroshi Nagashima, Morio Matsumoto

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number24413
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016 Apr 14

Fingerprint

Marfan Syndrome
Swine
Fibroblasts
Genome
Scoliosis
Funnel Chest
Technology Transfer
Inborn Genetic Diseases
Epiphyses
Elastic Tissue
Sudden Death
Extracellular Matrix
Animal Models
Quality of Life
Fibrillin-1
Phenotype
Incidence

ASJC Scopus subject areas

  • General

Cite this

Generation of heterozygous fibrillin-1 mutant cloned pigs from genome-edited foetal fibroblasts. / Umeyama, Kazuhiro; Watanabe, Koota; Watanabe, Masahito; Horiuchi, Keisuke; Nakano, Kazuaki; Kitashiro, Masateru; Matsunari, Hitomi; Kimura, Tokuhiro; Arima, Yoshimi; Sampetrean, Oltea; Nagaya, Masaki; Saito, Masahiro; Saya, Hideyuki; Kosaki, Kenjiro; Nagashima, Hiroshi; Matsumoto, Morio.

In: Scientific Reports, Vol. 6, 24413, 14.04.2016.

Research output: Contribution to journalArticle

Umeyama, K, Watanabe, K, Watanabe, M, Horiuchi, K, Nakano, K, Kitashiro, M, Matsunari, H, Kimura, T, Arima, Y, Sampetrean, O, Nagaya, M, Saito, M, Saya, H, Kosaki, K, Nagashima, H & Matsumoto, M 2016, 'Generation of heterozygous fibrillin-1 mutant cloned pigs from genome-edited foetal fibroblasts', Scientific Reports, vol. 6, 24413. https://doi.org/10.1038/srep24413
Umeyama, Kazuhiro ; Watanabe, Koota ; Watanabe, Masahito ; Horiuchi, Keisuke ; Nakano, Kazuaki ; Kitashiro, Masateru ; Matsunari, Hitomi ; Kimura, Tokuhiro ; Arima, Yoshimi ; Sampetrean, Oltea ; Nagaya, Masaki ; Saito, Masahiro ; Saya, Hideyuki ; Kosaki, Kenjiro ; Nagashima, Hiroshi ; Matsumoto, Morio. / Generation of heterozygous fibrillin-1 mutant cloned pigs from genome-edited foetal fibroblasts. In: Scientific Reports. 2016 ; Vol. 6.
@article{a1fec45fc202481dacd8bd150ebb4d63,
title = "Generation of heterozygous fibrillin-1 mutant cloned pigs from genome-edited foetal fibroblasts",
abstract = "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.",
author = "Kazuhiro Umeyama and Koota Watanabe and Masahito Watanabe and Keisuke Horiuchi and Kazuaki Nakano and Masateru Kitashiro and Hitomi Matsunari and Tokuhiro Kimura and Yoshimi Arima and Oltea Sampetrean and Masaki Nagaya and Masahiro Saito and Hideyuki Saya and Kenjiro Kosaki and Hiroshi Nagashima and Morio Matsumoto",
year = "2016",
month = "4",
day = "14",
doi = "10.1038/srep24413",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Generation of heterozygous fibrillin-1 mutant cloned pigs from genome-edited foetal fibroblasts

AU - Umeyama, Kazuhiro

AU - Watanabe, Koota

AU - Watanabe, Masahito

AU - Horiuchi, Keisuke

AU - Nakano, Kazuaki

AU - Kitashiro, Masateru

AU - Matsunari, Hitomi

AU - Kimura, Tokuhiro

AU - Arima, Yoshimi

AU - Sampetrean, Oltea

AU - Nagaya, Masaki

AU - Saito, Masahiro

AU - Saya, Hideyuki

AU - Kosaki, Kenjiro

AU - Nagashima, Hiroshi

AU - Matsumoto, Morio

PY - 2016/4/14

Y1 - 2016/4/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84963904083&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963904083&partnerID=8YFLogxK

U2 - 10.1038/srep24413

DO - 10.1038/srep24413

M3 - Article

C2 - 27074716

AN - SCOPUS:84963904083

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 24413

ER -