LMNA -mutated Rabbits: A Model of Premature Aging Syndrome with Muscular Dystrophy and Dilated Cardiomyopathy

Premature aging syndromes are rare genetic disorders mimicking clinical and molecular features of aging. Products of the gene, primarily lamin A and C, are major components of the nuclear lamina. A recently identified group of premature aging syndromes was related to mutations of the gene. Although...

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Bibliographic Details
Published in:Aging and disease 2019-02, Vol.10 (1), p.102-115
Main Authors: Sui, Tingting, Liu, Di, Liu, Tingjun, Deng, Jichao, Chen, Mao, Xu, Yuanyuan, Song, Yuning, Ouyang, Hongsheng, Lai, Liangxue, Li, Zhanjun
Format: Article
Language:English
Subjects:
Aging (Biology)
Backup software
Congestive cardiomyopathy
Gene mutation
Genes
Health aspects
Lipodystrophy
Messenger RNA
Muscular dystrophy
Myocardial diseases
Novels
Orginal
Rabbits
RNA
Skeletal muscle
Transcription (Genetics)
Walking
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Summary:Premature aging syndromes are rare genetic disorders mimicking clinical and molecular features of aging. Products of the gene, primarily lamin A and C, are major components of the nuclear lamina. A recently identified group of premature aging syndromes was related to mutations of the gene. Although disorders have been identified in premature aging syndromes, affect specifically the skeletal muscles, cardiac muscles, and lipodystrophy, understanding the pathogenic mechanisms still need to be elucidated. Here, to establish a rabbit knockout (KO) model of premature aging syndromes, we performed precise targeting in rabbits via co-injection of Cas9/sgRNA mRNA into zygotes. The -KO rabbits exhibited reduced locomotion activity with abnormal stiff walking posture and a shortened stature, all of them died within 22 days. In addition, cardiomyopathy, muscular dystrophy, bone and joint abnormalities, as well as lipodystrophy were observed in -KO rabbits. In conclusion, the novel rabbit -KO model, displayed typical features of histopathological defects that are observed in premature aging syndromes, and may be utilized as a valuable resource for understanding the pathophysiological mechanisms of premature aging syndromes and elucidating mysteries of the normal process of aging in humans.
ISSN:2152-5250
2152-5250
DOI:10.14336/AD.2018.0209