期刊
BRAIN
卷 132, 期 -, 页码 439-451出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/awn335
关键词
muscular dystrophy; fukutin related protein
资金
- Medical Research Council (UK)
- Muscular Dystrophy Campaign (UK)
- Association Francaise contres les Myopathies (AFM)
- Muscular Dystrophy Association (USA)
- MRC [G0601943, G0200171] Funding Source: UKRI
- Medical Research Council [G0200171, G0601943] Funding Source: researchfish
Mutations in fukutin related protein (FKRP) are responsible for a common group of muscular dystrophies ranging from adult onset limb girdle muscular dystrophies to severe congenital forms with associated structural brain involvement, including Muscle Eye Brain disease. A common feature of these disorders is the variable reduction in the glycosylation of skeletal muscle -dystroglycan. In order to gain insight into the pathogenesis and clinical variability, we have generated two lines of mice, the first containing a missense mutation and a neomycin cassette, FKRP-Neo(Tyr307Asn) and the second containing the FKRPTyr307Asn mutation alone. We have previously associated this missense mutation with a severe muscleeyebrain phenotype in several families. Homozygote Fkrp-Neo(Tyr307Asn) mice die soon after birth and show a reduction in the laminin-binding epitope of -dystroglycan in muscle, eye and brain, and have reduced levels of FKRP transcript. Homozygous Fkrp(Tyr307Asn) mice showed no discernible phenotype up to 6 months of age, contrary to the severe clinical course observed in patients with the same mutation. These results suggest the generation of a mouse model for FKRP related muscular dystrophy requires a knock-down rather than a knock-in strategy in order to give rise to a disease phenotype.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据