TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative diseases that show considerable clinical and pathologic overlap, with no effective treatments available. Mutations in the RNA binding protein TDP-43 were recently identified in patients with familial amyotrophic lateral sclerosis (ALS), and TDP-43 aggregates are found in both ALS and FTLD-U (FTLD with ubiquitin aggregates), suggesting a common underlying mechanism. We report that mice expressing a mutant form of human TDP-43 develop a progressive and fatal neurodegenerative disease reminiscent of both ALS and FTLD-U. Despite universal transgene expression throughout the nervous system, pathologic aggregates…

• BW
  Burroughs Wellcome Fund
• MD
  Muscular Dystrophy Association
• CD
  Children's Discovery Institute
• HC
  Hope Center for Neurological Disorders
• NI
  National Institutes of Health

  Awards: NS055980, NS057105