B6SJL-Tg(Thy1-TARDBP*G298S)S97Pcw/J

Stock number: 017589
Product name: Thy1.2-TDP43*G298S line S97
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

Transgenic mice expressing full-length mutant(G298S) human TARDBP exhibit a late onset motor neuron disease. These mice may be useful for studying amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease).

Detailed description

These TARDBP transgenic mice express a full-length mutant (G298S) human TAR DNA binding protein (TARDBP) cDNA directed by the mouse Thy1 promoter. The TARDBP gene product, TDP-43, is localized to the nucleus of nerve cells. Accumulations of mutant TDP-43 have been linked to the development of motor neuron diseases such as Lou Gehrig's disease (Amyotrophic lateral sclerosis; ALS) and frontotemporal lobar degeneration. Mice hemizygous for the transgene develop a late onset motor neuron disease characterized by loss of large motor neurons, denervation muscle atrophy and paralysis. In 2012, the donating investigator's laboratory reported that homozygous mice are viable but survive less than four months. The Jackson Laboratory Repository has not attempted to generate homozygous mice to date (March 2015).

Development

The Thy1.2-TDP43*G298S transgene was designed in the laboratory of Dr. Philip C. Wong (Johns Hopkins University). The transgene contains the mouse Thy1 (thymus cell antigen 1, theta, promoter (Thy1.2)) promoter driving expression of the full-length human TAR DNA binding protein (TARDBP) cDNA sequence. A missense mutation associated with amyotrophic lateral sclerosis (ALS) was introduced at position 298 results in a glycine-to-serine substitution (G298S). The resulting transgene was microinjected into B6SJL/F1 oocytes and mice from founder line S97 were maintained on a B6SJL/F1 background.

In 2014, one hemizygous male with agouti coat color was sent to The Jackson Laboratory Repository. Upon arrival, sperm was cryopreserved. To generate the living colony, an aliquot of the frozen sperm was used to fertilize oocytes from B6SJLF1/J mice (Stock No. 100012).

Allele

Symbol: Tg(Thy1-TARDBP*G298S)S97Pcw
Name: transgene insertion S97, Philip C Wong
MGI accession ID: MGI:5308398
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Thy1-TARDBP*G298S)S97Pcw
Marker name: transgene insertion S97, Philip C Wong
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F1
Expressed genes: TARDBP,TAR DNA binding protein,human
Molecular note: This transgene contains the mouse Thy1 (thymus cell antigen 1, theta, promoter (Thy1.2)) promoter driving expression of the full-length human TAR DNA binding protein (TARDBP) cDNA sequence. A missense mutation associated with amyotrophic lateral sclerosis (ALS) was introduced at position 298 results in a glycine-to-serine substitution (G298S). Line S97 was established.