Analysis of RNA metabolism in peripheral WBCs of TDP-43 KI mice identifies novel biomarkers of ALS
| Autor: | Chikako Hara-Miyauchi, Kenji Sakimura, Minami Hasegawa, Hirotaka James Okano, Hiroki Ohta, Hideyuki Okano |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Programmed cell death Pathology medicine.medical_specialty Cell Survival TDP-43 Neuroscience(all) Mutant SMN1 Biology 03 medical and health sciences 0302 clinical medicine Tar (tobacco residue) Gene knockin mental disorders Leukocytes medicine Animals Humans Gene Knock-In Techniques RNA Messenger Amyotrophic lateral sclerosis Motor Neurons RNA metabolism Messenger RNA General Neuroscience Amyotrophic Lateral Sclerosis nutritional and metabolic diseases Biomarker General Medicine medicine.disease Molecular biology Mice Mutant Strains nervous system diseases DNA-Binding Proteins 030104 developmental biology Mutation RNA Biomarker (medicine) ALS Peripheral blood cells Apoptosis Regulatory Proteins Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience Research. 106:12-22 |
| ISSN: | 0168-0102 |
| Popis: | Diagnostic biomarkers for amyotrophic lateral sclerosis (ALS) have yet to be identified. One of the causes of neuronal cell death in neurodegenerative diseases is abnormal RNA metabolism, although the mechanisms by which this occurs are unclear. Detection of abnormal RNA metabolism in white blood cells (WBCs) could lead to a new biomarker of ALS onset. TAR DNA-binding protein 43kDa (TDP-43) is an RNA-binding protein that regulates RNA metabolism. We previously developed a mouse model of ALS that exhibits adult-onset motor dysfunction; these mutant TDP-43 knock in (KI) mice heterozygously express mutant human TDP-43 (A382T or G348C). In the present study, we examined TDP-43 mRNA levels in WBCs of KI mice and found that A382T mutant mRNA is significantly higher than G348C. Our results suggest that each mutant TDP-43 induces distinct RNA metabolism, and that the expression of total TDP-43 alone in WBC is not suitable as an ALS biomarker. To identify additional candidates, we focused on survival and apoptosis-related factors and examined their mRNA metabolism in WBCs. mRNA levels of both Smn1 and Naip5 correlated with TDP-43 levels and also differed between A382T and G348C. Together, TDP-43 and these factors may enable detection of abnormalities in individual ALS pathologies. |
| Databáze: | OpenAIRE |
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