title: The artificial gene Jazz, a transcriptional regulator of utrophin, corrects the dystrophic pathology in mdx mice.
abstract: The absence of the cytoskeletal protein dystrophin results in Duchenne muscular dystrophy (DMD). The utrophin protein is the best candidate for dystrophin replacement in DMD patients. To obtain therapeutic levels of utrophin expression in dystrophic muscle, we developed an alternative strategy based on the use of artificial zinc finger transcription factors (ZF ATFs). The ZF ATF 'Jazz' was recently engineered and tested in vivo by generating a transgenic mouse specifically expressing Jazz at the muscular level. To validate the ZF ATF technology for DMD treatment we generated a second mouse model by crossing Jazz-transgenic mice with dystrophin-deficient mdx mice. Here, we show that the artificial Jazz protein restores sarcolemmal integrity and prevents the development of the dystrophic disease in mdx mice. This exclusive animal model establishes the notion that utrophin-based therapy for DMD can be efficiently developed using ZF ATF technology and candidates Jazz as a novel therapeutic molecule for DMD therapy.
authors: Istituto di Neurobiologia e Medicina Molecolare, CNR, IRCCS Fondazione S. Lucia, 00143 Rome, Italy.
authors: Maria Grazia
authors: MG
authors: Di Certo
authors: Nicoletta
authors: N
authors: Corbi
authors: Georgios
authors: G
authors: Strimpakos
authors: Annalisa
authors: A
authors: Onori
authors: Siro
authors: S
authors: Luvisetto
authors: Cinzia
authors: C
authors: Severini
authors: Angelo
authors: A
authors: Guglielmotti
authors: Enrico Maria
authors: EM
authors: Batassa
authors: Cinzia
authors: C
authors: Pisani
authors: Aristide
authors: A
authors: Floridi
authors: Barbara
authors: B
authors: Benassi
authors: Maurizio
authors: M
authors: Fanciulli
authors: Armando
authors: A
authors: Magrelli
authors: Elisabetta
authors: E
authors: Mattei
authors: Claudio
authors: C
authors: Passananti
mesh_terms: D000818:Animals; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014157:Transcription Factors / Q000235:genetics*; D049411:Utrophin / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D016189:Dystrophin; D014157:Transcription Factors; D049411:Utrophin