Heterogeneity of Matrin 3 in the developing and aging murine central nervous system

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• 作者：Sruti Rayaprolu ; Simon D' ; Alton ; Keith Crosby ; Christina Moloney ; John Howard ; Colin Duffy ; Mariela Cabrera ; Zoe Siemienski ; Abigail R. Hernandez ; Carolina Gallego-Iradi ; David R. Borchelt and Jada Lewis
• 刊名：Journal of Comparative Neurology
• 出版年：2016
• 出版时间：October 01, 2016
• 年：2016
• 卷：524
• 期：14
• 页码：2740-2752
• 全文大小：7611K
• ISSN：1096-9861

文摘

Mutations in the <em>MATR3em> gene encoding the nucleotide binding protein Matrin 3 have recently been identified as causing a subset of familial amyotrophic lateral sclerosis (fALS) and more rarely causing distal myopathy. Translating the identification of <em>MATR3em> mutations into an understanding of disease pathogenesis and the creation of mouse models requires a complete understanding of normal Matrin 3 levels and distribution <em>in vivoem>. Consequently, we examined the levels of murine Matrin 3 in body tissues and regions of the central nervous system (CNS). We observed a significant degree of variability in Matrin 3 protein levels among different tissues of adult animals, with the highest levels found in reproductive organs and the lowest in muscle. Within the adult CNS, Matrin 3 levels were lowest in spinal cord. Further, we found that Matrin 3 declines significantly in CNS through early development and young adulthood before stabilizing. As previously reported, antibodies to Matrin 3 primarily stain nuclei, but the intensity of staining was not uniform in all nuclei. The low levels of Matrin 3 in spinal cord and muscle could mean that that these tissues are particularly vulnerable to alterations in Matrin 3 function. Our study is the first to characterize endogenous Matrin 3 in rodents across the lifespan, providing the groundwork for deciphering disease mechanisms and developing mouse models of <em>MATR3em>-linked ALS. J. Comp. Neurol. 524:2740–2752, 2016.