Genetic biomarkers for ALS disease in transgenic SOD1 G93A mice

Calvo, A.C. (Universidad de Zaragoza) ; Manzano, R. (Universidad de Zaragoza) ; Atencia-Cibreiro, G. ; Oliván, S. (Universidad de Zaragoza) ; Muñoz, M.J. (Universidad de Zaragoza) ; Zaragoza, P. (Universidad de Zaragoza) ; Cordero-Vázquez, P. ; Esteban-Pérez, J. ; García-Redondo, A. ; Osta, R. (Universidad de Zaragoza)

Resumen: The pathophysiological mechanisms of both familial and sporadic Amyotrophic Lateral Sclerosis (ALS) are unknown, although growing evidence suggests that skeletal muscle tissue is a primary target of ALS toxicity. Skeletal muscle biopsies were performed on transgenic SOD1G93A mice, a mouse model of ALS, to determine genetic biomarkers of disease longevity. Mice were anesthetized with isoflurane, and three biopsy samples were obtained per animal at the three main stages of the disease. Transcriptional expression levels of seventeen genes, Ankrd1, Calm1, Col19a1, Fbxo32, Gsr, Impa1, Mef2c, Mt2, Myf5, Myod1, Myog, Nnt, Nogo A, Pax7, Rrad, Sln and Snx10, were tested in each muscle biopsy sample. Total RNA was extracted using TRIzol Reagent according to the manufacturer's protocol, and variations in gene expression were assayed by real-time PCR for all of the samples. The Pearson correlation coefficient was used to determine the linear correlation between transcriptional expression levels throughout disease progression and longevity. Consistent with the results obtained from total skeletal muscle of transgenic SOD1G93A mice and 74-day-old denervated mice, five genes (Mef2c, Gsr, Col19a1, Calm1 and Snx10) could be considered potential genetic biomarkers of longevity in transgenic SOD1G93A mice. These results are important because they may lead to the exploration of previously unexamined tissues in the search for new disease biomarkers and even to the application of these findings in human studies.

Idioma: Inglés

DOI: 10.1371/journal.pone.0032632

Año: 2012

Publicado en: PloS one 7, 3 (2012), e32632 [10 pp]
ISSN: 1932-6203

Factor impacto JCR: 3.73 (2012)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 7 / 57 = 0.123 (2012) - Q1 - T1

Financiación: info:eu-repo/grantAgreement/ES/ISCIII/EC08-00049
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI07-1283
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI10-01787

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Farmacología (Dpto. Farmacología y Fisiolog.)
Área (Departamento): Proy. investigación DDA (Dpto. Anatom.,Embri.Genét.Ani.)