B6;C3-Tg(tetO-TARDBP*)4Vle/J

Stock number: 014650
Product name: tetO-hTDP-43-ΔNLS line 4
Research areas: Neurobiology Research, Research Tools

Description

This transgenic strain can be used to generate bitransgenic mice with spatio-temporal specific inducible overexpression of the mutant hTDP-43-deltaNLS protein, which may be useful for studies of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).

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Detailed description

These transgenic mice express the mutant human TARDBP, TAR DNA binding protein, hTDP-43-deltaNLS, with a defective nuclear localization signal, under the direction of the tetO, tetracycline operator promoter. Mice hemizygous for the transgenic insert are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. It is not known if homozygotes are viable. When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of the hTDP-43-deltaNLS protein may be regulated with tetracycline or its analog doxycycline (DOX) in the double mutant offspring.
When mated to Camk2a-tTA mice which express tTA in forebrain neurons (See for example: Stock No. 003010; Stock No. 007004; Stock No. 010712), the resulting bitransgenic mice exhibit progressive neurodegeneration in the cortex and hippocampus, corticospinal tract degeneration, gliosis and spastic motor impairment. One month after DOX removal, bitransgenic mice have lost approximately 50% of hippocampal dentate gyrus neurons.

Development

A transgenic construct containing the mutant human TARDBP, TAR DNA binding protein, hTDP-43-deltaNLS, under the direction of the tetO, tetracycline operator promoter was injected into fertilized C57BL/6J x C3HeJ F1 mouse eggs. Founder line 4 was subsequently established. The mice were bred to wildtype B6C3F1/Crl mice and maintained as hemizygotes. Upon arrival at The Jackson Laboratory Repository, the mice were bred with B6C3F1/J hybrid mice (Stock No. 100010) for at least one generation to establish the colony.

Allele

Symbol: Tg(tetO-TARDBP*)4Vle
Name: transgene insertion 4, Virginia M Y Lee
MGI accession ID: MGI:5000261
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence; Humanized sequence
Synonyms: hTDP-43deltaNLS4
Marker symbol: Tg(tetO-TARDBP*)4Vle
Marker name: transgene insertion 4, Virginia M Y Lee
Chromosome: UN
Strain of origin: (C57BL/6J x C3H/HeJ)F1
Expressed genes: TARDBP,TAR DNA binding protein,human
Site of expression: When bred to mice expressing tetracycline transactivator (tTA), tetracycline or its analog doxycycline (DOX) administration results in the expression of mutant human TARDBP, TAR DNA binding protein, hTDP-43-deltaNLS in transactivator expressing tissues of the offspring.
Molecular note: The tetracycline responsive promoter drives inducible expression of the human cDNA lacking the nuclear localization signal. Two lines were generated (4 and 19).