also known as Lou Gehrig's disease) and frontotemporal lobar degeneration (FTLD) are clinically quite distinct, although a few patients have some overlapping symptoms. However, both conditions are characterized by aggregates that contain the protein TDP-43 in the cytoplasm (the jelly-like substance that fills the cell) of nerve cells in the brain and spinal cord. Surprisingly, Virginia Lee and colleagues, at the University of Pennsylvania School of Medicine, Philadelphia, have now determined, using mice expressing either normal human TDP-43 or a mutant form of human TDP-43 that localized to the cytoplasm rather than the nucleus (the normal location for the protein), that the presence of TDP-43 cytoplasmic aggregates do not correlate with nerve cell death. Rather, nerve cell death correlated with loss of mouse TDP-43 in the nucleus, which led to profound alterations in gene expression. These data provide new insight into the link between TDP-43 and neurological disease.
TITLE: Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice
Virginia M.-Y. Lee
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: 215.662.6427; Fax: 215.349.5909; E-mail: firstname.lastname@example.org.
View this article at: http://www.jci.org/articles/view/44867?key=5fcbdccd59ebc8a3542e
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