C57BL/6-Tg(Prnp-TARDBP)3cPtrc/J

Stock number: 016608
Product name: TDP-43_PrP
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

TDP-43_PrP transgenic mice express a full length wild type human TARDBP cDNA under control of a Prnp promoter. These transgenic mice may be useful in studying neuromuscular and neurodegenerative disorders such as ALS (Lou Gehrig's Disease).

Detailed description

TDP-43_PrP transgenic mice express a full length wild type human TAR DNA binding protein (TARDBP or TDP-43) cDNA under control of the prion protein (Prnp) promoter. Hemizygotes are viable, fertile, and normal in size. TDP-43 is a ubiquinated protein localized to the nucleus of cells. Accumulations of TDP-43 are involved in the development of Amyotrophic lateral sclerosis (ALS). These mice express wildtype human TDP-43 primarily in the nuclei of neurons throughout much of the gray matter of the spinal cord and brain, including the hippocampus, striatum, brainstem and cortex. Homozygotes and hemizygous express TDP-43 in brain at 2.5 and 1.9-fold endogenous TDP-43 levels, respectively. Endogenous TDP-43 is down-regulated in response to transgene overexpression. Beginning at 14 days of age, homozygous TDP-43_PrP are smaller than hemizygous littermates. By 21 days of age homozygotes develop body tremors, have difficulty walking, and develop an aberrant "swimming" gait. Between 1 and 2 months of age they become unable to right themselves. These also mice exhibit reactive gliosis, and axonal and myelin degeneration. These mice exhibit truncated TDP-43 and ubiquitin aggregates containing phosphorylated TDP-43. Hemizygous mice are indistinguishable from wildtype littermates. 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.

Development

The TDP-43_PrP transgene was designed with the human TARDBP gene driven by a mouse prion protein (Prnp) promoter. The transgene was microinjected into fertilized C57BL/6 oocytes. Mice from the highest expressing founder line were bred to C57BL/6 mice to establish a colony. Upon arrival at The Jackson Laboratory, transgenic mice were bred to C57BL/6J mice (Stock No. 000664).

Allele

Symbol: Tg(Prnp-TARDBP)3cPtrc
Name: transgene insertion 3c, Leonard Petrucelli
MGI accession ID: MGI:5002476
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: TDP-43^PrP; Tg(Prnp-TARDBP)3cLtrc
Marker symbol: Tg(Prnp-TARDBP)3cPtrc
Marker name: transgene insertion 3c, Leonard Petrucelli
Chromosome: UN
Strain of origin: C57BL/6
Expressed genes: TARDBP,TAR DNA binding protein,human
Molecular note: The TDP-43PrP transgene was designed with the human TAR DNA binding protein (TARDBP or TDP-43) gene driven by a mouse prion protein (Prnp) promoter. Line 3c was generated.