title: CFTR-deficient pigs display peripheral nervous system defects at birth.
abstract: Peripheral nervous system abnormalities, including neuropathy, have been reported in people with cystic fibrosis. These abnormalities have largely been attributed to secondary manifestations of the disease. We tested the hypothesis that disruption of the cystic fibrosis transmembrane conductance regulator (CFTR) gene directly influences nervous system function by studying newborn CFTR(-/-) pigs. We discovered CFTR expression and activity in Schwann cells, and loss of CFTR caused ultrastructural myelin sheath abnormalities similar to those in known neuropathies. Consistent with neuropathic changes, we found increased transcripts for myelin protein zero, a gene that, when mutated, can cause axonal and/or demyelinating neuropathy. In addition, axon density was reduced and conduction velocities of the trigeminal and sciatic nerves were decreased. Moreover, in vivo auditory brainstem evoked potentials revealed delayed conduction of the vestibulocochlear nerve. Our data suggest that loss of CFTR directly alters Schwann cell function and that some nervous system defects in people with cystic fibrosis are likely primary.
authors: Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
authors: Leah R
authors: LR
authors: Reznikov
authors: Qian
authors: Q
authors: Dong
authors: Jeng-Haur
authors: JH
authors: Chen
authors: Thomas O
authors: TO
authors: Moninger
authors: Jung Min
authors: JM
authors: Park
authors: Yuzhou
authors: Y
authors: Zhang
authors: Jianyang
authors: J
authors: Du
authors: Michael S
authors: MS
authors: Hildebrand
authors: Richard J H
authors: RJ
authors: Smith
authors: Christoph O
authors: CO
authors: Randak
authors: David A
authors: DA
authors: Stoltz
authors: Michael J
authors: MJ
authors: Welsh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons; D001483:Base Sequence; D002490:Central Nervous System / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers; D008297:Male; D009186:Myelin Sheath / Q000235:genetics / Q000473:pathology; D017933:Peripheral Nervous System / Q000378:metabolism / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D013552:Swine
chemical_list: D017931:DNA Primers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
references: J Med Case Rep. 2011 Aug 12;5:366
references: 21838874
references: Pain. 2012 Aug;153(8):1763-1768
references: 22704856
references: Neurosci Biobehav Rev. 2007;31(5):728-51
references: 17445892
references: J Cyst Fibros. 2006 Aug;5(3):187-91
references: 16627012
references: Brain. 1996 Jun;119 ( Pt 3):741-53
references: 8673487
references: Eur Neurol. 1991;31(2):77-81
references: 2044620
references: Science. 2008 Sep 26;321(5897):1837-41
references: 18818360
references: Ir J Med Sci. 1995 Jul-Sep;164(3):207-8
references: 7672935
references: Am J Respir Cell Mol Biol. 1993 Feb;8(2):201-8
references: 7678968
references: Neurobiol Dis. 2007 Oct;28(1):39-51
references: 17659877
references: J Cell Biol. 2000 Mar 6;148(5):1021-34
references: 10704451
references: J Clin Invest. 2008 Apr;118(4):1571-7
references: 18324337
references: J Biol Chem. 2009 Aug 21;284(34):23146-58
references: 19546221
references: J Biol Chem. 2010 Jun 11;285(24):18928-38
references: 20400506
references: J Neurol Neurosurg Psychiatry. 1999 Aug;67(2):174-9
references: 10406984
references: Brain. 2003 Jan;126(Pt 1):134-51
references: 12477701
references: N Engl J Med. 1980 Jun 26;302(26):1453-6
references: 6246430
references: Neurology. 1998 Mar;50(3):799-801
references: 9521281
references: J Physiol. 1993 Oct;470:501-20
references: 7508507
references: Mol Pharmacol. 2006 Sep;70(3):851-9
references: 16760362
references: Eur J Med Genet. 2011 Nov-Dec;54(6):e580-3
references: 21787890
references: J Chronic Dis. 1983;36(3):269-78
references: 6298269
references: Am Rev Respir Dis. 1984 Jun;129(6):911-4
references: 6329048
references: Lab Invest. 2009 Jun;89(6):636-44
references: 19333236
references: Pediatrics. 1981 Aug;68(2):187-94
references: 7267224
references: Neurogastroenterol Motil. 2004 Apr;16 Suppl 1:143-7
references: 15066021
references: J Clin Neurophysiol. 2010 Jun;27(3):216-8
references: 20461013
references: Dev Med Child Neurol. 1996 Jan;38(1):59-64
references: 8606017
references: J Neuropathol Exp Neurol. 2003 Jul;62(7):751-64
references: 12901701
references: J Neuropathol Exp Neurol. 2010 Dec;69(12):1256-69
references: 21107138
references: Proc Am Thorac Soc. 2004;1(1):47-53
references: 16113412
references: Hum Mol Genet. 2011 Jun 1;20(11):2081-90
references: 21363884
references: Hum Mol Genet. 2007 Dec 15;16(24):2991-3001
references: 17855448
references: Physiol Rev. 1999 Jan;79(1 Suppl):S3-S22
references: 9922374
references: Neurology. 1996 May;46(5):1318-24
references: 8628474
references: Science. 1985 Sep 27;229(4720):1407-8
references: 4035357
references: J Neurol Neurosurg Psychiatry. 1999 Jun;66(6):779-82
references: 10329755
references: N Engl J Med. 2005 May 12;352(19):1992-2001
references: 15888700
references: J Gen Physiol. 2004 Aug;124(2):125-37
references: 15277574
references: Semin Pediatr Surg. 2009 Nov;18(4):196-205
references: 19782301
references: Am J Pathol. 1994 Sep;145(3):640-9
references: 8080046
references: J Neurol Neurosurg Psychiatry. 2000 Dec;69(6):806-11
references: 11080237
references: J Neurosci. 2000 Jun 1;20(11):4120-8
references: 10818147
references: Neuroreport. 1994 Aug 15;5(13):1684-8
references: 7529593
references: J Cell Biol. 2004 May 24;165(4):565-73
references: 15148307
references: Acta Neuropathol. 2000 Sep;100(3):299-304
references: 10965800
references: Clin Chest Med. 2007 Jun;28(2):331-46
references: 17467552
references: Continuum (Minneap Minn). 2012 Feb;18(1):39-59
references: 22810069
references: Sci Transl Med. 2010 Apr 28;2(29):29ra31
references: 20427821
references: J Pediatr. 1988 Oct;113(4):637-40
references: 3171788
references: Ann Neurol. 2012 Jan;71(1):84-92
references: 22275255
references: Br J Dermatol. 2010 Nov;163(5):1082-4
references: 20560957
references: J Neurosci Methods. 2010 Mar 15;187(1):33-40
references: 20034518
references: Thorax. 1987 Jul;42(7):538-41
references: 3438897
references: Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20571-5
references: 21059918
references: Nature. 2000 May 25;405(6785):458-62
references: 10839541
references: Mol Cell Neurosci. 2004 Feb;25(2):241-51
references: 15019941