Technical Details:
JHU scientists have developed conditional knockout mice and embryonic stem cell models. The purpose was to study the physiological role of Tat activating regulatory DNA-binding protein (Tardbp or TDP-43). This protein is highly conserved in metazoan and has been linked to the pathophysiology of amyotrophic lateral sclerosis and frontal temporal lobar degeneration and is essential for early embryonic development. Researchers showed that TDP-43 regulates one specific target Tbc1d1, a gene associated with human obesity. This indicates that TDP-43 plays a crucial role in controlling energy metabolism. Thus, these conditional Tardbp knockout mice offer a useful animal model to study the effects of TDP-43 on obesity and diabetes. It is also known that some individuals with amyotrophic lateral sclerosis show a hypermetabolic state that may contribute to the pathogenesis of amyotrophic lateral sclerosis. Therefore, the conditional Tardbp knockout model system is useful to examine the role of this protein in the neurons of brain and spinal cord, which is critical for the understanding of the pathogenic mechanism of frontal temporal dementia and amyotrophic lateral sclerosis.
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Publications/Associated Cases:
Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16320-4
