Quantitative immuno-mass spectrometry imaging of skeletal muscle dystrophin
| Autor: | Philip Doble, Nerida Cole, Stanley F. Nelson, Rachelle H. Crosbie, Jonathan Wanagat, Elizabeth M. Gibbs, M. Carrie Miceli, Florian Barthélémy, Mika T. Westerhausen, Thomas E. Lockwood, David P. Bishop |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Pathology Duchenne muscular dystrophy Muscle Fibers Skeletal Fluorescent Antibody Technique Gadolinium Gene mutation Mass Spectrometry Quadriceps Muscle Dystrophin Mice 0302 clinical medicine 80 and over Muscular Dystrophy Child Aged 80 and over Pediatric Multidisciplinary biology Skeletal Immunohistochemistry medicine.anatomical_structure Medicine Biomedical Imaging Female musculoskeletal diseases Duchenne/ Becker Muscular Dystrophy medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Adolescent Science Intellectual and Developmental Disabilities (IDD) Bioengineering Muscle Fibers Mass spectrometry imaging Article 03 medical and health sciences Rare Diseases medicine Genetics Animals Humans Aged Biophysical methods business.industry Skeletal muscle Diagnostic markers medicine.disease Duchenne Brain Disorders Muscular Dystrophy Duchenne 030104 developmental biology Tissue sections Musculoskeletal Mutation biology.protein business 030217 neurology & neurosurgery |
| Zdroj: | Scientific reports, vol 11, iss 1 Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) Scientific Reports |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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