Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Compromised Muscle Properties in a Severe Hypophosphatasia Murine Model
International journal of molecular sciences, v 24(21), 15905
01 Nov 2023
PMID: 37958888
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hypophosphatasia (HPP) is a rare metabolic bone disorder characterized by low levels of tissue non-specific alkaline phosphatase (TNAP) that causes under-mineralization of the bone, leading to bone deformity and fractures. In addition, patients often present with chronic muscle pain, reduced muscle strength, and an altered gait. In this work, we explored dynamic muscle function in a homozygous TNAP knockout mouse model of severe juvenile onset HPP. We found a reduction in skeletal muscle size and impairment in a range of isolated muscle contractile properties. Using histological methods, we found that the structure of HPP muscles was similar to healthy muscles in fiber size, actin and myosin structures, as well as the α-tubulin and mitochondria networks. However, HPP mice had significantly fewer embryonic and type I fibers than wild type mice, and fewer metabolically active NADH+ muscle fibers. We then used oxygen respirometry to evaluate mitochondrial function and found that complex I and complex II leak respiration were reduced in HPP mice, but that there was no disruption in efficiency of electron transport in complex I or complex II. In summary, the severe HPP mouse model recapitulates the muscle strength impairment phenotypes observed in human patients. Further exploration of the role of alkaline phosphatase in skeletal muscle could provide insight into mechanisms of muscle weakness in HPP.
Metrics
Details
- Title
- Compromised Muscle Properties in a Severe Hypophosphatasia Murine Model
- Creators
- Emily G Pendleton - University of GeorgiaAnna S Nichenko - University of GeorgiaJennifer Mcfaline-Figueroa - University of GeorgiaChristiana J Raymond-Pope - University of MinnesotaAlbino G Schifino - University of GeorgiaTaylor M Pigg - University of GeorgiaRuth P Barrow - University of GeorgiaSarah M Greising - University of MinnesotaJarrod A Call - University of GeorgiaLuke J Mortensen - University of Georgia
- Publication Details
- International journal of molecular sciences, v 24(21), 15905
- Publisher
- MDPI
- Grant note
- R21 EB027802 / NIBIB NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physical Therapy (and Rehabilitation Sciences)
- Web of Science ID
- WOS:001100411800001
- Scopus ID
- 2-s2.0-85176545494
- Other Identifier
- 991022030046204721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Multidisciplinary