Quantitative immuno-mass spectrometry imaging of skeletal muscle dystrophin
Bishop, DP
Westerhausen, MT
Barthelemy, F
Lockwood, T
Cole, N
Gibbs, EM
Crosbie, RH
Nelson, SF
Miceli, MC
Doble, PA
Wanagat, J
- Publisher:
- Nature Publishing Group
- Publication Type:
- Journal Article
- Citation:
- Scientific Reports, 2021, 11, (1), pp. 1-11
- Issue Date:
- 2021-01-13
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Bishop, DP | |
dc.contributor.author | Westerhausen, MT | |
dc.contributor.author | Barthelemy, F | |
dc.contributor.author |
Lockwood, T https://orcid.org/0000-0001-7030-1341 |
|
dc.contributor.author | Cole, N | |
dc.contributor.author | Gibbs, EM | |
dc.contributor.author | Crosbie, RH | |
dc.contributor.author | Nelson, SF | |
dc.contributor.author | Miceli, MC | |
dc.contributor.author | Doble, PA | |
dc.contributor.author | Wanagat, J | |
dc.date.accessioned | 2022-01-18T23:42:23Z | |
dc.date.available | 2020-12-22 | |
dc.date.available | 2022-01-18T23:42:23Z | |
dc.date.issued | 2021-01-13 | |
dc.identifier.citation | Scientific Reports, 2021, 11, (1), pp. 1-11 | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/10453/153302 | |
dc.description.abstract | Emerging and promising therapeutic interventions for Duchenne muscular dystrophy (DMD) are confounded by the challenges of quantifying dystrophin. Current approaches have poor precision, require large amounts of tissue, and are difficult to standardize. This paper presents an immuno-mass spectrometry imaging method using gadolinium (Gd)-labeled anti-dystrophin antibodies and laser ablation-inductively coupled plasma-mass spectrometry to simultaneously quantify and localize dystrophin in muscle sections. Gd is quantified as a proxy for the relative expression of dystrophin and was validated in murine and human skeletal muscle sections following k-means clustering segmentation, before application to DMD patients with different gene mutations where dystrophin expression was measured up to 100 µg kg−1 Gd. These results demonstrate that immuno-mass spectrometry imaging is a viable approach for pre-clinical to clinical research in DMD. It rapidly quantified relative dystrophin in single tissue sections, efficiently used valuable patient resources, and may provide information on drug efficacy for clinical translation. | |
dc.format | Electronic | |
dc.language | eng | |
dc.publisher | Nature Publishing Group | |
dc.relation | http://purl.org/au-research/grants/arc/DE180100194 | |
dc.relation | http://purl.org/au-research/grants/arc/DP190102361 | |
dc.relation | US Department of Health and Human Services1R21AR072950-01A1 | |
dc.relation | Australian-American Fulbright Commission | |
dc.relation.ispartof | Scientific Reports | |
dc.relation.isbasedon | 10.1038/s41598-020-80495-8 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject.mesh | Adolescent | |
dc.subject.mesh | Aged, 80 and over | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Child | |
dc.subject.mesh | Dystrophin | |
dc.subject.mesh | Female | |
dc.subject.mesh | Fluorescent Antibody Technique | |
dc.subject.mesh | Gadolinium | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Immunohistochemistry | |
dc.subject.mesh | Male | |
dc.subject.mesh | Mass Spectrometry | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Muscle Fibers, Skeletal | |
dc.subject.mesh | Muscular Dystrophy, Duchenne | |
dc.subject.mesh | Mutation | |
dc.subject.mesh | Quadriceps Muscle | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Muscular Dystrophy, Duchenne | |
dc.subject.mesh | Gadolinium | |
dc.subject.mesh | Dystrophin | |
dc.subject.mesh | Fluorescent Antibody Technique | |
dc.subject.mesh | Immunohistochemistry | |
dc.subject.mesh | Mutation | |
dc.subject.mesh | Adolescent | |
dc.subject.mesh | Aged, 80 and over | |
dc.subject.mesh | Child | |
dc.subject.mesh | Female | |
dc.subject.mesh | Male | |
dc.subject.mesh | Quadriceps Muscle | |
dc.subject.mesh | Mass Spectrometry | |
dc.subject.mesh | Muscle Fibers, Skeletal | |
dc.title | Quantitative immuno-mass spectrometry imaging of skeletal muscle dystrophin | |
dc.type | Journal Article | |
utslib.citation.volume | 11 | |
utslib.location.activity | England | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Strength - CFS - Centre for Forensic Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences | |
utslib.copyright.status | open_access | * |
pubs.consider-herdc | false | |
dc.date.updated | 2022-01-18T23:42:16Z | |
pubs.issue | 1 | |
pubs.publication-status | Published | |
pubs.volume | 11 | |
utslib.citation.issue | 1 |
Abstract:
Emerging and promising therapeutic interventions for Duchenne muscular dystrophy (DMD) are confounded by the challenges of quantifying dystrophin. Current approaches have poor precision, require large amounts of tissue, and are difficult to standardize. This paper presents an immuno-mass spectrometry imaging method using gadolinium (Gd)-labeled anti-dystrophin antibodies and laser ablation-inductively coupled plasma-mass spectrometry to simultaneously quantify and localize dystrophin in muscle sections. Gd is quantified as a proxy for the relative expression of dystrophin and was validated in murine and human skeletal muscle sections following k-means clustering segmentation, before application to DMD patients with different gene mutations where dystrophin expression was measured up to 100 µg kg−1 Gd. These results demonstrate that immuno-mass spectrometry imaging is a viable approach for pre-clinical to clinical research in DMD. It rapidly quantified relative dystrophin in single tissue sections, efficiently used valuable patient resources, and may provide information on drug efficacy for clinical translation.
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