title: Gene profiling of embryonic skeletal muscle lacking type I ryanodine receptor Ca(2+) release channel.
abstract: In mature skeletal muscle, the intracellular Ca(2+) concentration rises dramatically upon membrane depolarization, constituting the link between excitation and contraction. This process requires Ca(2+) release from the sarcoplasmic reticulum via the type 1 ryanodine receptor (RYR1). However, RYR1's potential roles in muscle development remain obscure. We used an established RyR1- null mouse model, dyspedic, to investigate the effects of the absence of a functional RYR1 and, consequently, the lack of RyR1-mediated Ca(2+) signaling, during embryogenesis. Homozygous dyspedic mice die after birth and display small limbs and abnormal skeletal muscle organization. Skeletal muscles from front and hind limbs of dyspedic fetuses (day E18.5) were subjected to microarray analyses, revealing 318 differentially expressed genes. We observed altered expression of multiple transcription factors and members of key signaling pathways. Differential regulation was also observed for genes encoding contractile as well as muscle-specific structural proteins. Additional qRT-PCR analysis revealed altered mRNA levels of the canonical muscle regulatory factors Six1, Six4, Pax7, MyoD, MyoG and MRF4 in mutant muscle, which is in line with the severe developmental retardation seen in dyspedic muscle histology analyses. Taken together, these findings suggest an important non-contractile role of RyR1 or RYR1-mediated Ca(2+) signaling during muscle organ development.
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty of the University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: Dilyana
authors.initials: D
authors.lastname: Filipova
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty of the University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Walter
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, Medical Faculty of the University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: John A
authors.initials: JA
authors.lastname: Gaspar
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Brunn
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty of the University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: Nina F
authors.initials: NF
authors.lastname: Linde
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty of the University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: Ardestani
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Deckert
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, Medical Faculty of the University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty of the University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pfitzer
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Neurophysiology, Medical Faculty of the University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: Agapios
authors.initials: A
authors.lastname: Sachinidis
authors.affiliation: Center of Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty of the University of Cologne, Robert-Koch-Str. 39, Cologne 50931, Germany.
authors.forename: Symeon
authors.initials: S
authors.lastname: Papadopoulos
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D004622:Embryo, Mammalian / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D019837:Ryanodine Receptor Calcium Release Channel / Q000172:deficiency*
chemical_list: D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C000592747:ryanodine receptor 1, mouse
references.citation: Nature. 1994 Jun 16;369(6481):556-9
references.pmid: 7515481
references.citation: Am J Physiol Cell Physiol. 2000 May;278(5):C998-C1010
references.pmid: 10794674
references.citation: Int J Mol Sci. 2015;16(1):1066-95
references.pmid: 25569087
references.citation: Nat Cell Biol. 2012 Feb;14(2):186-91
references.pmid: 22179044
references.citation: Cell Calcium. 1994 May;15(5):356-68
references.pmid: 8033194
references.citation: Commun Integr Biol. 2008;1(1):4-5
references.pmid: 19704446
references.citation: BMC Bioinformatics. 2006;7:85
references.pmid: 16504059
references.citation: J Cell Biol. 1991 Jul;114(1):125-41
references.pmid: 1646821
references.citation: Genes Dev. 2005 Jul 15;19(14):1715-22
references.pmid: 16024660
references.citation: J Biol Chem. 1997 Mar 14;272(11):7360-7
references.pmid: 9054435
references.citation: Amyotroph Lateral Scler. 2011 Jul;12(4):250-6
references.pmid: 21375368
references.citation: Matrix Biol. 2014 Jul;37:35-48
references.pmid: 24589453
references.citation: Hum Mutat. 2006 Oct;27(10):977-89
references.pmid: 16917943
references.citation: J Invest Dermatol. 2008 Apr;128(4):871-81
references.pmid: 17943183
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D818-24
references.pmid: 24163257
references.citation: Cell Physiol Biochem. 2014;33(2):249-72
references.pmid: 24525559
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10803-8
references.pmid: 8855261
references.citation: Pathol Int. 2003 Oct;53(10):653-8
references.pmid: 14516314
references.citation: J Invest Dermatol. 2004 Apr;122(4):885-91
references.pmid: 15102077
references.citation: J Biol Chem. 2001 Jun 22;276(25):22868-74
references.pmid: 11301324
references.citation: J Cell Biol. 2010 Mar 22;188(6):833-49
references.pmid: 20308426
references.citation: Antioxid Redox Signal. 2011 Jul 1;15(1):205-18
references.pmid: 21050144
references.citation: Bioinformatics. 2003 Jan 22;19(2):185-93
references.pmid: 12538238
references.citation: Biophys J. 1975 Jul;15(7):707-23
references.pmid: 806311
references.citation: Physiol Genomics. 2008 Jan 17;32(2):207-18
references.pmid: 18000159
references.citation: PLoS One. 2009;4(11):e7934
references.pmid: 19936205
references.citation: Trends Cell Biol. 2012 Nov;22(11):602-9
references.pmid: 22944199
references.citation: Oncogene. 2004 Apr 12;23(16):2838-49
references.pmid: 15077147
references.citation: Mol Biol Cell. 2009 Feb;20(3):846-58
references.pmid: 19037100
references.citation: J Mol Biol. 2003 Nov 7;333(5):951-64
references.pmid: 14583192
references.citation: Dev Dyn. 2001 Feb;220(2):155-62
references.pmid: 11169848
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18537-42
references.pmid: 18003898
references.citation: BMC Bioinformatics. 2013;14:128
references.pmid: 23586463
references.citation: Stat Appl Genet Mol Biol. 2004;3:Article3
references.pmid: 16646809
references.citation: Hum Mol Genet. 2003 Apr 1;12(7):739-48
references.pmid: 12651869
references.citation: Am J Physiol Cell Physiol. 2003 Jun;284(6):C1438-47
references.pmid: 12529240
references.citation: Mol Syndromol. 2010 Sep;1(3):99-112
references.pmid: 21031079
references.citation: Invest Ophthalmol Vis Sci. 2012 Jan;53(1):461-9
references.pmid: 21989719
references.citation: J Biol Chem. 2012 Nov 30;287(49):41560-8
references.pmid: 23071115
references.citation: Cancer Biol Ther. 2004 Feb;3(2):156-61
references.pmid: 14764989
references.citation: J Gen Physiol. 2012 Aug;140(2):235-41
references.pmid: 22802359
references.citation: J Cell Physiol. 2006 Nov;209(2):379-88
references.pmid: 16897752
references.citation: J Neurocytol. 1993 Nov;22(11):955-65
references.pmid: 7507977
references.citation: J Biomed Biotechnol. 2011;2011:569628
references.pmid: 22028589
references.citation: Cell Calcium. 2014 Nov;56(5):390-6
references.pmid: 25224502
references.citation: Cold Spring Harb Perspect Biol. 2012 Feb;4(2). pii: a008342. doi: 10.1101/cshperspect.a008342
references.pmid: 22300977
references.citation: BMC Genomics. 2011;12:602
references.pmid: 22165895
references.citation: J Cell Sci. 2001 Oct;114(Pt 20):3673-83
references.pmid: 11707519
references.citation: Nat Protoc. 2009;4(1):44-57
references.pmid: 19131956
references.citation: Physiol Rev. 2004 Apr;84(2):649-98
references.pmid: 15044685
references.citation: Physiol Rev. 2000 Jul;80(3):1215-65
references.pmid: 10893434
references.citation: Methods Cell Biol. 1997;52:283-306
references.pmid: 9379955
references.citation: J Biol Chem. 2010 Apr 30;285(18):13781-7
references.pmid: 20207743