title: Rodent models of TDP-43: recent advances.
abstract: Recently, missense mutations in the gene TARDBP encoding TDP-43 have been linked to familial ALS. The discovery of genes encoding these RNA binding proteins, such as TDP-43 and FUS/TLS, raised the notion that altered RNA metabolism is a major factor underlying the pathogenesis of ALS. To begin to unravel how mutations in TDP-43 cause dysfunction and death of motor neurons, investigators have employed both gain- and loss-of-function studies in rodent model systems. Here, we will summarize major findings from the initial sets of TDP-43 transgenic and knockout rodent models, identify their limitations, and point to future directions toward clarification of disease mechanism(s) and testing of therapeutic strategies that ultimately may lead to novel therapy for this devastating disease. This article is part of a Special Issue entitled RNA-Binding Proteins.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: William
authors.initials: W
authors.lastname: Tsao
authors.forename: Yun Ha
authors.initials: YH
authors.lastname: Jeong
authors.forename: Sophie
authors.initials: S
authors.lastname: Lin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ling
authors.forename: Donald L
authors.initials: DL
authors.lastname: Price
authors.forename: Po-Min
authors.initials: PM
authors.lastname: Chiang
authors.forename: Philip C
authors.initials: PC
authors.lastname: Wong
mesh_terms: D050154:Adiposity / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D057177:TDP-43 Proteinopathies / Q000235:genetics* / Q000473:pathology*
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA