STOCK Tg(Prnp-TARDBP)4Jlel/J

Stock number: 016144
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

TDP43 transgenic mice express a full-length human TAR DNA binding protein (TARDBP) cDNA under the control of mouse prion protien promoter. These transgenic mice may be useful in studying neuromuscular and neurodegenerative disorders such as ALS (Lou Gehrig's Disease) and frontotemporal lobar degeneration with ubiquitin aggregates.

Detailed description

TDP43 transgenic mice express a full length human TAR DNA binding protein (TARDBP or TDP-43) cDNA inserted between exon 2 and exon 3 of the mouse prion protein (Prnp) gene. The transgene in founder line 4 was later found to have integrated on the X chromosome. Hemizygotes are viable and fertile, with mean survival of 109 days. TDP-43 is a ubiquinated protein localized to the nucleus of nerve cells. Accumulations of mutated TDP-43 are involved in the development of Amyotrophic lateral sclerosis (ALS). These mice express human TDP-43 in the spinal cord and skeletal muscle. They exhibit progressive neurodegeneration characterized by bilateral proximal weakness, spasticity, reduced spontaneous movements and progressive weight loss. Variable phenotype penetrance is observed and some animals remain asymptomatic at 6 months of age. These mice contain a nuclear localized, less truncated form of TDP-43 than that observed in TDP-43*A315T mice (Stock No. 016143). Disease progression is later than that observed in TDP-43*A315T mice.

Development

A full-length human TAR DNA binding protein (TARDBP or TDP-43) cDNA sequence was inserted between exon 2 and exon 3 of mouse prion protein (PrP or Prnp) gene at two unique XhoI sites in the Mo-Prp.Xho plasmid vector (ATCC#JHU-2). The resulting transgene was microinjected into B6SJLF1 oocytes and mice from founder line 4, in which the transgene integrated on the X chromosome, were bred with CD1 mice to establish a colony. These mice were maintained on a mixed background. Upon arrival at The Jackson Laboratory, transgenic mice were bred with non-transgenic littermates to establish the colony.

Allele

Symbol: Tg(Prnp-TARDBP)4Jlel
Name: transgene insertion 4, Jeffrey L Elliott
MGI accession ID: MGI:4839645
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: WT TDP-43 line 4
Marker symbol: Tg(Prnp-TARDBP)4Jlel
Marker name: transgene insertion 4, Jeffrey L Elliott
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F1
Expressed genes: TARDBP,TAR DNA binding protein,human
Molecular note: The mouse promoter drives neuronal expression of the wild-type human cDNA. Several lines were established (including 4, 13, and 21).