In support of this hypothesis, it has been reported that the RNA-binding protein muscleblind-like 1 is sequestered into nuclear Selleck LEE011 foci of accumulated mutant RNA in both DM1 and DM2 [8]. As muscleblind-like 1 controls pre-mRNA splicing [9], a loss of function of this protein may induce disruption of several gene transcripts leading to many of the cell functional defects that underlie the DM1 and DM2 phenotypes [10–12]. It should be noted,

however, that DM cardinal features and splicing defects have been reproduced in DM1 models even in the absence of ribonuclear foci [13,14]. On the other hand, although DM1 and DM2 phenotypes are very similar, they are not identical. For instance, a congenital form has been observed only in DM1; moreover, weakness primarily affects distal muscles in DM1 and proximal muscles in DM2. Finally, we and others have recently recognized specific histopathological features that allow differentiation of the two entities by means of muscle biopsy analysis [15,16]. It is possible that some of these differences are accounted for by mechanisms other than RNA toxicity. The observation that homozygosity does not appear to affect disease severity, both in DM1 and DM2, argues against haploinsufficiency as a pathogenic

mechanism of the DM [17–19]. Nonetheless, DMPK haploinsufficiency has been demonstrated in DM1 muscle [20,21], and DMPK-deficient mice show a late-onset, skeletal myopathy [22], and heart conduction defects similar to those observed Selleck MK2206 in DM1 patients [23]. It is therefore possible that some cardiac and skeletal muscle clinical features in DM1 are determined by a reduced abundance and/or defective function of the DMPK protein product.

A similar scenario has been proposed for DM2 after characterizing the phenotype of ZNF9+/− mice [24]. Zinc finger protein 9 is a small protein of 19 kDa containing seven zinc finger domains of the CCHC type and exhibits striking sequence similarities to retroviral nucleic acid-binding protein (CNBP) [25]. ZNF9/CNBP is highly conserved at the amino acid and nucleotide levels in human, mouse, rat, chicken and frog [26–29] Oxymatrine and is expressed in a variety of tissues in chicken [28,30]. Although ZNF9/CNBP has been implicated in several processes [25,31,32], its cellular localization and function are still unclear [29,33]. In order to clarify whether ZNF9 may play a specific role in myofibres, the precise subcellular localization of this protein has to be assessed. The aim of the present study was therefore to establish: (i) the level of expression of ZNF9 in different rat tissues and in human skeletal muscle; and (ii) the subcellular localization of ZNF9 in normal and DM2 human muscles.