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Cystic fibrosis (CF) is an autosomal recessive disorder that predominantly affects individuals of Northern European descent, occurring at a rate of 1 in 3500. It is caused by a genetic mutation in a gene on chromosome 7, most commonly the ΔF508 mutation, that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This results in thicker mucus secretions and obstruction pathologies in multiple organs, including the lungs and sinuses.
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Related Experiment Video

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In vitro Measurements of Tracheal Constriction Using Mice
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Abnormal tracheal smooth muscle function in the CF mouse.

Helen L Wallace1, Kevin W Southern2, Marilyn G Connell2

  • 1Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool Liverpool, U.K.

Physiological Reports
|January 9, 2014
PubMed
Summary
This summary is machine-generated.

Cystic fibrosis (CF) airways show reduced smooth muscle contractility, not due to muscle changes, but a specific pathway downregulation affecting acetylcholine activation. This impacts airway hyperresponsiveness in CF mice.

Keywords:
Contractioncystic fibrosissmooth muscletrachea

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Area of Science:

  • Pulmonary Medicine
  • Cellular Biology
  • Physiology

Background:

  • Airway smooth muscle (ASM) contractility is linked to airway hyperresponsiveness (AHR).
  • ASM anomalies in cystic fibrosis (CF) airways are reported but not fully understood.
  • Mechanisms driving CF airway smooth muscle dysfunction are largely unknown.

Purpose of the Study:

  • To investigate ASM contractility and morphology in adult CF mouse tracheas.
  • To identify underlying cellular pathway alterations in CF ASM.
  • To characterize CF trachea morphology during development.

Main Methods:

  • Examined adult CF mouse tracheal ring preparations for contractility.
  • Assessed ASM morphology in adult tracheas and embryonic lung cultures.
  • Investigated cellular pathways involved in ASM contractility.
  • Measured tracheal caliber and luminal areas in CF and wild-type mice.

Main Results:

  • CF mouse tracheas exhibited reduced caliber, fewer cartilage rings, and smaller cross-sectional/luminal areas.
  • No significant differences were found in ASM area or distribution between CF and wild-type mice.
  • CF tracheas showed a reduced amplitude and duration of contraction to carbachol, specific to acetylcholine (ACh) pathway activation.

Conclusions:

  • CF mouse tracheas display diminished contractile capacity, linked to ACh pathway downregulation.
  • This loss of contractility is not associated with alterations in ASM quantity or distribution.
  • Findings suggest a specific functional deficit in CF ASM contractility independent of structural changes.