MODELING TDP-43 PROTEINOPATHY

Described herein is the discovery that neither the nuclear localization signal (NLS) nor the prion-like domain (PLD) of TDP-43 is necessary for embryonic stem cell culture and differentiation into motor neurons in vitro. The ability of ES cells to express these TDP-43 mutants and differentiate into...

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Bibliographische Detailangaben
Hauptverfasser:	Frendewey, David, Sharma-Kanning, Aarti, Zambrowicz, Brian
Format:	Patent
Sprache:	eng
Schlagworte:	AGRICULTURE ANIMAL HUSBANDRY BEER BIOCHEMISTRY CARE OF BIRDS, FISHES, INSECTS CHEMISTRY COMPOSITIONS THEREOF CULTURE MEDIA ENZYMOLOGY FISHING FORESTRY HUMAN NECESSITIES HUNTING HYGIENE MEDICAL OR VETERINARY SCIENCE METALLURGY MICROBIOLOGY MICROORGANISMS OR ENZYMES MUTATION OR GENETIC ENGINEERING NEW BREEDS OF ANIMALS ORGANIC CHEMISTRY PEPTIDES PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR SPIRITS TRAPPING VINEGAR WINE
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Beschreibung
Zusammenfassung:	Described herein is the discovery that neither the nuclear localization signal (NLS) nor the prion-like domain (PLD) of TDP-43 is necessary for embryonic stem cell culture and differentiation into motor neurons in vitro. The ability of ES cells to express these TDP-43 mutants and differentiate into motor neurons that exhibit an ALS-like phenotype whereby the TDP-43 mutants redistribute to and aggregate in the cytoplasm and fail to regulate cryptic exon splicing allows these cells to act as a model of TDP-43 proteinopathy for the testing of candidate therapeutic agents that may resolve such proteinopathy. Additionally, these ES cells may be used to successfully generate non-human animals, e.g., mice, that also exhibit hallmark symptoms of ALS and that may be used in testing candidate agents useful in treating TDP-43 proteinopathies.