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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Virginia M Lee, University of Pennsylvania
Genetic Background | Generation |
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?+pN2F7
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Allele Type |
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Transgenic (Inducible, Inserted expressed sequence, Humanized sequence) |
Starting at:
$270.00 Domestic price for female 4-week |
348.51 Domestic price for breeder pair |
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.
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.
Expressed Gene | TARDBP, TAR DNA binding protein, human |
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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. |
Allele Name | transgene insertion 4, Virginia M Y Lee |
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Allele Type | Transgenic (Inducible, Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | hTDP-43deltaNLS4 |
Gene Symbol and Name | Tg(tetO-TARDBP*)4Vle, transgene insertion 4, Virginia M Y Lee |
Gene Synonym(s) | |
Promoter | tetO, tet operator, |
Expressed Gene | 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. |
Strain of Origin | (C57BL/6J x C3H/HeJ)F1 |
Chromosome | UN |
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). |
Mutations Made By | Susan Leight, University of Pennsylvania |
When maintaining a live colony, hemizygous (carrier) mice may be bred with wildtype (noncarrier) mice from the colony or with B6C3F1/J hybrid mice (Stock No. 100010). It is not known if homozygotes are viable.
When using the tetO-hTDP-43-ΔNLS line 4 mouse strain in a publication, please cite the originating article(s) and include JAX stock #014650 in your Materials and Methods section.
Service/Product | Description | Price |
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Hemizygous or Non carrier for Tg(tetO-TARDBP*)4Vle |
Frozen Mouse Embryo | B6;C3-Tg(tetO-TARDBP*)4Vle/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;C3-Tg(tetO-TARDBP*)4Vle/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;C3-Tg(tetO-TARDBP*)4Vle/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6;C3-Tg(tetO-TARDBP*)4Vle/J Frozen Embryo | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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