Reference Report

Reference
Citation	Chartier, A., Benoit, B., Simonelig, M. (2006). A Drosophila model of oculopharyngeal muscular dystrophy reveals intrinsic toxicity of PABPN1. EMBO J. 25(10): 2253--2262. (Export to RIS)
FlyBase ID	FBrf0190356
Publication Type	Research paper
PubMed ID	16642034
PubMed Abstract	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.
DOI	10.1038/sj.emboj.7601117
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Language of Publication	English
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Publication Type	Journal
Abbreviation	EMBO J.
Title	The EMBO Journal
Publication Year	1982-
ISBN/ISSN	0261-4189
Data from Reference
Alleles (18)
	BacA\p35^Scer\UAS.cHa DnaJ-1^Scer\UAS.cKa Hsap\HSPA1L^Scer\UAS.cWa Hsap\PABPN1^{17ala.Scer\UAS} Hsap\PABPN1^{dm.17ala.Scer\UAS} Hsap\PABPN1^Scer\UAS.cCa Hsap\PABPN1^{Δala.Scer\UAS} Hsap\PABPN1^{ΔCLD.17ala.Scer\UAS} Hsap\PABPN1^{ΔC-term.17ala.Scer\UAS} Hsap\PABPN1^{ΔRRM.17ala.Scer\UAS} Hsc70-4^Scer\UAS.cEa Hsp70Ab^EY01148 Hsp83^e6A Scer\GAL4^da.G32 Scer\GAL4^how-24B Scer\GAL4^Mhc.PW Tpr2^Scer\UAS.cKa w^+mC
Constructs (14)
	P{GAL4-da.G32} P{GAL4-Mhc.W} P{UAS-DnaJ-1.K} P{UAS-Hsap\HSPA1L.W} P{UAS-Hsc70-4.WT} P{UAS-p35.H} P{UAS-PABPN1.17ala} P{UAS-PABPN1.17ala-dm} P{UAS-PABPN1.17ala-ΔCLD} P{UAS-PABPN1.17ala-ΔC-term} P{UAS-PABPN1.17ala-ΔRRM} P{UAS-PABPN1.C} P{UAS-PABPN1.Δala} P{UAS-Tpr2.K}
Genes (16)
	BacA\p35 DnaJ-1 Hsap\HSPA1L Hsap\PABPN1 Hsc70-4 Hsp70Aa Hsp70Ab Hsp70Ba Hsp70Bb Hsp70Bbb Hsp70Bc Hsp83 Pabp2 Scer\GAL4 Tpr2 w
Insertions (2)
	P{EPgy2}Hsp70Ab^EY01148 P{GawB}how^24B
Natural transposons (1)
	P-element