کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3069775 1580701 2010 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Progressive motor weakness in transgenic mice expressing human TDP-43
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Progressive motor weakness in transgenic mice expressing human TDP-43
چکیده انگلیسی

Familial ALS patients with TDP-43 gene mutations and sporadic ALS patients share common TDP-43 neuronal pathology. To delineate mechanisms underlying TDP-43 proteinopathies, transgenic mice expressing A315T, M337V or wild type human TDP-43 were generated. Multiple TDP-43 founders developed a severe early motor phenotype that correlated with TDP-43 levels in spinal cord. Three A315T TDP-43 lines developed later onset paralysis with cytoplasmic ubiquitin inclusions, gliosis and TDP-43 redistribution and fragmentation. The WT TDP-43 mouse line with highest spinal cord expression levels remains asymptomatic, although these mice show spinal cord pathology. One WT TDP-43 line with high skeletal muscle levels of TDP-43 developed a severe progressive myopathy. Over-expression of TDP-43 in vivo is sufficient to produce progressive motor phenotypes by a toxic gain of function paradigm. Transgenic mouse lines expressing untagged mutant and wild type TDP-43 under the same promoter represent a powerful new model system for studying TDP-43 proteinopathies in vivo.

Research highlights
► Generation of transgenic mice expressing human A315T, M337V or wild type TDP-43;
► Early post natal weakness and paralysis in both mutant and wild type founders;
► Propagating A315T TDP-43 lines develop progressive weakness with CNS pathology;
► CNS pathology has cytoplasmic ubiquitin inclusions and TDP-43 fragmentation; and
► Over-expression of wild type TDP-43 in muscle produces a severe myopathy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 40, Issue 2, November 2010, Pages 404–414
نویسندگان
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