title: Sequestration of MBNL1 in tissues of patients with myotonic dystrophy type 2.
abstract: The pathogenesis of myotonic dystrophy type 2 includes the sequestration of MBNL proteins by expanded CCUG transcripts, which leads to an abnormal splicing of their target pre-mRNAs. We have found CCUG(exp) RNA transcripts of the ZNF9 gene associated with the formation of ribonuclear foci in human skeletal muscle and some non-muscle tissues present in muscle biopsies and skin excisions from myotonic dystrophy type 2 patients. Using RNA-FISH and immunofluorescence-FISH methods in combination with a high-resolution confocal microscopy, we demonstrate a different frequency of nuclei containing the CCUG(exp) foci, a different expression pattern of MBNL1 protein and a different sequestration of MBNL1 by CCUG(exp) repeats in skeletal muscle, vascular smooth muscle and endothelia, Schwann cells, adipocytes, and ectodermal derivatives. The level of CCUG(exp) transcription in epidermal and hair sheath cells is lower compared with that in other tissues examined. We suppose that non-muscle tissues of myotonic dystrophy type 2 patients might be affected by a similar molecular mechanism as the skeletal muscle, as suggested by our observation of an aberrant insulin receptor splicing in myotonic dystrophy type 2 adipocytes.
authors.affiliation: Institute of Pathology, Brno Faculty Hospital, Brno, Czech Republic. zlukas@nbox.cz
authors.forename: Z
authors.initials: Z
authors.lastname: Lukáš
authors.forename: M
authors.initials: M
authors.lastname: Falk
authors.forename: J
authors.initials: J
authors.lastname: Feit
authors.forename: O
authors.initials: O
authors.lastname: Souček
authors.forename: I
authors.initials: I
authors.lastname: Falková
authors.forename: L
authors.initials: L
authors.lastname: Štefančíková
authors.forename: E
authors.initials: E
authors.lastname: Janoušová
authors.forename: L
authors.initials: L
authors.lastname: Fajkusová
authors.forename: J
authors.initials: J
authors.lastname: Zaorálková
authors.forename: R
authors.initials: R
authors.lastname: Hrabálková
mesh_terms: D000199:Actins / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000704:Analysis of Variance; D018952:Antigens, CD34 / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000378:metabolism*; D020967:Myotonic Disorders / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009223:Myotonic Dystrophy; D016900:Neurofilament Proteins / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D012313:RNA / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D009418:S100 Proteins / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: D000199:Actins; D018952:Antigens, CD34; C433227:CNBP protein, human; C493663:MBNL1 protein, human; D016900:Neurofilament Proteins; D016601:RNA-Binding Proteins; D009418:S100 Proteins; D012313:RNA; D011972:Receptor, Insulin