A muscleblind knockout model for myotonic dystrophy

被引：564

作者：

Kanadia, RN

Johnstone, KA

Mankodi, A

Lungu, C

Thornton, CA

Esson, D

Timmers, AM

Hauswirth, WW

Swanson, MS ^{[1
]}

机构：

[1] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA

[2] Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA

[3] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA

来源：

SCIENCE | 2003年 / 302卷 / 5652期

关键词：

D O I：

10.1126/science.1088583

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The neuromuscular disease myotonic dystrophy (DM) is caused by microsatellite repeat expansions at two different genomic loci. Mutant DM transcripts are retained in the nucleus together with the muscleblind (Mbnl) proteins, and these abnormal RNAs somehow interfere with pre-mRNA splicing regulation. Here, we show that disruption of the mouse Mbnl1 gene leads to muscle, eye, and RNA splicing abnormalities that are characteristic of DM disease. Our results support the hypothesis that manifestations of DM can result from sequestration of specific RNA binding proteins by a repetitive element expansion in a mutant RNA.

引用

页码：1978 / 1980

页数：3

共 25 条

[1] The muscleblind gene participates in the organization of Z-bands and epidermal attachments of Drosophila muscles and is regulated by Dmef2
Artero, R
Prokop, A
Paricio, N
Begemann, G
Pueyo, I
Mlodzik, M
Perez-Alonso, M
Baylies, MK
[J]. DEVELOPMENTAL BIOLOGY, 1998, 195 (02) : 131 - 143
[2] Begemann G, 1997, DEVELOPMENT, V124, P4321
[3] DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model
Berul, CI
Maguire, CT
Aronovitz, MJ
Greenwood, J
Miller, C
Gehrmann, J
Housman, D
Mendelsohn, ME
Reddy, S
[J]. JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (04) : R1 - R7
[4] Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing
Charlet-B, N
Savkur, RS
Singh, G
Philips, AV
Grice, EA
Cooper, TA
[J]. MOLECULAR CELL, 2002, 10 (01) : 45 - 53
[5] Expansion of a CUG trinucleotide repeat in the 3' untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts
Davis, BM
McCurrach, ME
Taneja, KL
Singer, RH
Housman, DE
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (14) : 7388 - 7393
[6] Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells
Fardaei, M
Rogers, MT
Thorpe, HM
Larkin, K
Hamshere, MG
Harper, PS
Brook, JD
[J]. HUMAN MOLECULAR GENETICS, 2002, 11 (07) : 805 - 814
[7] In vivo co-localisation of MBNL protein with DMPK expanded-repeat transcripts
Fardaei, M
Larkin, K
Brook, JD
Hamshere, MG
[J]. NUCLEIC ACIDS RESEARCH, 2001, 29 (13) : 2766 - 2771
[8] Pre-mRNA splicing and human disease
Faustino, NA
Cooper, TA
[J]. GENES & DEVELOPMENT, 2003, 17 (04) : 419 - 437
[9] CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus
Filippova, GN
Thienes, CP
Penn, BH
Cho, DH
Hu, YJ
Moore, JM
Klesert, T
Lobanenkov, VV
Tapscott, SJ
[J]. NATURE GENETICS, 2001, 28 (04) : 335 - 343
[10] Harper P.S., 1989, MYOTONIC DYSTROPHY

← 1 2 3 →