PMID- 16642034
OWN - NLM
STAT- MEDLINE
DCOM- 20060721
LR  - 20211020
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 25
IP  - 10
DP  - 2006 May 17
TI  - A Drosophila model of oculopharyngeal muscular dystrophy reveals intrinsic 
      toxicity of PABPN1.
PG  - 2253-62
AB  - Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset syndrome 
      characterized by progressive degeneration of particular muscles. OPMD is caused 
      by short GCG repeat expansions within the gene encoding the nuclear 
      poly(A)-binding protein 1 (PABPN1) that extend an N-terminal polyalanine tract in 
      the protein. Mutant PABPN1 aggregates as nuclear inclusions in OMPD patient 
      muscles. We have created a Drosophila model of OPMD that recapitulates the 
      features of the human disorder: progressive muscle degeneration, with muscle 
      defects proportional to the number of alanines in the tract, and formation of 
      PABPN1 nuclear inclusions. Strikingly, the polyalanine tract is not absolutely 
      required for muscle degeneration, whereas another domain of PABPN1, the 
      RNA-binding domain and its function in RNA binding are required. This 
      demonstrates that OPMD does not result from polyalanine toxicity, but from an 
      intrinsic property of PABPN1. We also identify several suppressors of the OPMD 
      phenotype. This establishes our OPMD Drosophila model as a powerful in vivo test 
      to understand the disease process and develop novel therapeutic strategies.
FAU - Chartier, Aymeric
AU  - Chartier A
AD  - Genetique du Developpement de la Drosophile, Institut de Genetique Humaine, CNRS 
      UPR 1142, Montpellier Cedex 5, France.
FAU - Benoit, Beatrice
AU  - Benoit B
FAU - Simonelig, Martine
AU  - Simonelig M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060427
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Molecular Chaperones)
RN  - 0 (Poly(A)-Binding Protein I)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Disease Models, Animal
MH  - Drosophila melanogaster/anatomy & histology/*physiology
MH  - Humans
MH  - Molecular Chaperones/metabolism
MH  - Muscle, Skeletal/anatomy & histology/metabolism/pathology
MH  - *Muscular Dystrophy, Oculopharyngeal/genetics/pathology/physiopathology
MH  - Phenotype
MH  - Poly(A)-Binding Protein I/genetics/*metabolism
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Wings, Animal/anatomy & histology
PMC - PMC1462976
EDAT- 2006/04/28 09:00
MHDA- 2006/07/22 09:00
PMCR- 2007/05/17
CRDT- 2006/04/28 09:00
PHST- 2005/10/13 00:00 [received]
PHST- 2006/04/04 00:00 [accepted]
PHST- 2006/04/28 09:00 [pubmed]
PHST- 2006/07/22 09:00 [medline]
PHST- 2006/04/28 09:00 [entrez]
PHST- 2007/05/17 00:00 [pmc-release]
AID - 7601117 [pii]
AID - 10.1038/sj.emboj.7601117 [doi]
PST - ppublish
SO  - EMBO J. 2006 May 17;25(10):2253-62. doi: 10.1038/sj.emboj.7601117. Epub 2006 Apr 
      27.