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01-04-2010 | Original Paper

Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis

Authors: Brian C. Kraemer, Theresa Schuck, Jeanna M. Wheeler, Linda C. Robinson, John Q. Trojanowski, Virginia M. Y. Lee, Gerard D. Schellenberg

Published in: Acta Neuropathologica | Issue 4/2010

Abstract

Abnormal TDP-43 aggregation is a prominent feature in the neuropathology of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Mutations in TARDBP, the gene encoding TDP-43, cause some cases of ALS. The normal function of TDP-43 remains incompletely understood. To better understand TDP-43 biology, we generated mutant mice carrying a genetrap disruption of Tardbp. Mice homozygous for loss of TDP-43 are not viable. TDP-43 deficient embryos die about day 7.5 of embryonic development thereby demonstrating that TDP-43 protein is essential for normal prenatal development and survival. However, heterozygous Tardbp mutant mice exhibit signs of motor disturbance and muscle weakness. Compared with wild type control littermates, Tardbp ^+/− animals have significantly decreased forelimb grip strength and display deficits in a standard inverted grid test despite no evidence of pathologic changes in motor neurons. Thus, TDP-43 is essential for viability, and mild reduction in TDP-43 function is sufficient to cause motor deficits without degeneration of motor neurons.

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Title: Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis
Authors: Brian C. Kraemer
Theresa Schuck
Jeanna M. Wheeler
Linda C. Robinson
John Q. Trojanowski
Virginia M. Y. Lee
Gerard D. Schellenberg
Publication date: 01-04-2010
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 4/2010
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-010-0659-0

At a glance: The STEP trials

Springer Medicine

Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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