CFTR-deficient pigs display peripheral nervous system defects at birth

Leah R Reznikov; Qian Dong; Jeng-Haur Chen; Thomas O Moninger; Jung Min Park; Yuzhou Zhang; Jianyang Du; Michael S Hildebrand; Richard J H Smith; Christoph O Randak; David A Stoltz; Michael J Welsh

doi:10.1073/pnas.1222729110

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CFTR-deficient pigs display peripheral nervous system defects at birth

Journal article

Open access

Peer reviewed

CFTR-deficient pigs display peripheral nervous system defects at birth

Leah R Reznikov, Qian Dong, Jeng-Haur Chen, Thomas O Moninger, Jung Min Park, Yuzhou Zhang, Jianyang Du, Michael S Hildebrand, Richard J H Smith, Christoph O Randak, …

Proceedings of the National Academy of Sciences - PNAS, Vol.110(8), pp.3083-3088

02/19/2013

DOI: 10.1073/pnas.1222729110

PMCID: PMC3581923

PMID: 23382208

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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.

Polymerase Chain Reaction

Animals, Newborn

Central Nervous System - metabolism

Myelin Sheath - pathology

Peripheral Nervous System - physiopathology

Cystic Fibrosis Transmembrane Conductance Regulator - physiology

Male

Cystic Fibrosis Transmembrane Conductance Regulator - metabolism

DNA Primers

Axons

Animals

Swine

Base Sequence

Myelin Sheath - genetics

Peripheral Nervous System - metabolism

Cystic Fibrosis Transmembrane Conductance Regulator - genetics

Details

Title: Subtitle: CFTR-deficient pigs display peripheral nervous system defects at birth
Creators: Leah R Reznikov - Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA
Qian Dong
Jeng-Haur Chen
Thomas O Moninger
Jung Min Park
Yuzhou Zhang
Jianyang Du
Michael S Hildebrand
Richard J H Smith
Christoph O Randak
David A Stoltz
Michael J Welsh
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.110(8), pp.3083-3088
DOI: 10.1073/pnas.1222729110
PMID: 23382208
PMCID: PMC3581923
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 1091-6490
eISSN: 1091-6490
Publisher: National Academy of Sciences; United States
Grant note: P30 ES005605 / NIEHS NIH HHS P01 HL091842 / NHLBI NIH HHS T32 HL007121 / NHLBI NIH HHS Howard Hughes Medical Institute T32 GM007337 / NIGMS NIH HHS T32HL007121-36 / NHLBI NIH HHS HL91842 / NHLBI NIH HHS
Language: English
Date published: 02/19/2013
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pulmonary Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurosurgery; Otolaryngology; Internal Medicine
Record Identifier: 9984006367802771

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