Related Experiment Video
Updated: Mar 5, 2026
08:59
Utilizing the Precision-Cut Lung Slice to Study the Contractile Regulation of Airway and Intrapulmonary Arterial Smooth Muscle
Published on: May 5, 2022
4.3K
Airway smooth muscle dysfunction in Pompe (Gaa ) mice
Allison M Keeler1,2, Donghai Liu3, Marina Zieger1,2
1Division of Pulmonary Medicine, Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts.
Summary
Pompe disease, caused by acid α-glucosidase (GAA) deficiency, impairs airway smooth muscle function. This glycogen accumulation in the trachea and bronchi contributes to respiratory insufficiency in affected individuals.
Area of Science:
- Pulmonary Medicine
- Genetics
- Biochemistry
Background:
- Pompe disease results from acid α-glucosidase (GAA) deficiency, leading to glycogen buildup in lysosomes.
- Skeletal and motor neuron pathology are known contributors to respiratory issues in Pompe disease.
- The role of lower airway pathology in Pompe disease-related respiratory insufficiency remains unevaluated.
Purpose of the Study:
- To investigate the impact of GAA deficiency on lower airway function in Pompe disease.
- To determine if glycogen accumulation in the trachea and bronchi contributes to respiratory insufficiency.
Main Methods:
- Utilized a Gaa-/- mouse model of Pompe disease.
- Compared histology, pulmonary mechanics, and airway smooth muscle (ASM) function between Gaa-/- and wild-type (WT) mice.
- Assessed calcium signaling during ASM contraction.
Main Results:
- Observed lysosomal glycogen accumulation in the smooth muscle of the trachea and bronchi in Gaa-/- mice.
- Gaa-/- mice exhibited hyporesponsive airway resistance and bronchial ring contraction to constrictors and a bronchodilator.
- Impaired calcium signaling during bronchiolar smooth muscle contraction was noted in Gaa-/- mice, indicating reduced extracellular calcium influx.
Conclusions:
- GAA enzyme deficiency causes glycogen accumulation in the trachea and bronchi.
- Lower airway smooth muscle dysfunction, including impaired calcium regulation, contributes to respiratory impairments in Pompe disease.
