These hTDP-43M337V transgenic mice express mutant human TARDBP protein under direction of the mouse prion protein (Prnp) promoter. They may be useful in studying neuromuscular and neurodegenerative disorders such as ALS (Lou Gehrig's Disease).
Leonard Petrucelli, Mayo Clinic
Genetic Background | Generation |
---|---|
|
Allele Type |
---|
Transgenic (Inserted expressed sequence, Humanized sequence) |
These hTDP-43M337V transgenic mice express a full length mutant human TAR DNA binding protein (TARDBP or TDP-43) cDNA under the direction of a mouse prion protein promoter. The cDNA is modified such that at codon 337, a methionine to replaced by a valine(M337V). The M337V mutation is associated with increased low molecular weight fragments, neuronal apoptosis and developmental delay in chick embryos. TDP-43 is a ubiquinated protein localized to the nucleus of cells. Accumulations of TDP-43 are associated with the development of Amyotrophic lateral sclerosis (ALS). Hemizygotes are viable, fertile, and normal in size, while homozygotes are initially viable with 70% dying within the first month of life. These mice express human TDP-43M337V primarily in the nuclei of neurons throughout much of the gray matter of the spinal cord and brain, including the brainstem and cortex. Homozygotes and hemizygous express TDP-43M337V in brain at 2.7 and 1.9-fold endogenous TDP-43 levels, respectively. Endogenous TDP-43 is down-regulated in response to transgene overexpression. By 21 days of age homozygotes develop body tremors, have difficulty walking, and develop an irregular "dragging" gait. By 1 month of age, homozygous TDP-43M337V mutants are smaller than hemizygous littermates, exhibit muscle weakness and become unable to right themselves. These mice exhibit reactive gliosis, and TDP-43M337V/ubiquitin aggregates containing phosphorylated TDP-43M337V. 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.
The hTDP-43M337V transgene was designed with the mouse prion protein (Prnp) promoter driving expression of a mutant form of the human TARDBP gene modified to have the methionine to valine substitution at codon 337 (M337V). The transgene was microinjected into fertilized C57BL/6 oocytes. Mice from the founder line 4 were bred to C57BL/6 mice to generate the hTDP-43M337V line 4 colony. Transgenic mice from line 4 were bred together, and then maintained by breeding homozygous mice together for several generations prior to sending to The Jackson Laboratory Repository. Upon arrival, transgenic mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation to establish the colony.
Expressed Gene | TARDBP, TAR DNA binding protein, human |
---|---|
Site of Expression |
Allele Name | transgene insertion 4, Leonard Petrucelli |
---|---|
Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | hTDP-43subM337V/sub; hTDP-43M337V line 4 |
Gene Symbol and Name | Tg(Prnp-TARDBP*M337V)4Ptrc, transgene insertion 4, Leonard Petrucelli |
Gene Synonym(s) | |
Promoter | Prnp, prion protein, mouse, laboratory |
Expressed Gene | TARDBP, TAR DNA binding protein, human |
Strain of Origin | C57BL/6 |
Chromosome | UN |
Molecular Note | The hTDP-43 |
Mutations Made By | Leonard Petrucelli, Mayo Clinic |
When maintaining a live colony, these mice may be bred as hemizygotes.
When using the C57BL/6-Tg(Prnp-TARDBP*M337V)4Ptrc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017604 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Hemizygous or Non Carrier for Tg(Prnp-TARDBP*M337V)4Ptrc |
Frozen Mouse Embryo | C57BL/6-Tg(Prnp-TARDBP*M337V)4Ptrc/J | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Tg(Prnp-TARDBP*M337V)4Ptrc/J | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Tg(Prnp-TARDBP*M337V)4Ptrc/J | $3373.50 |
Frozen Mouse Embryo | C57BL/6-Tg(Prnp-TARDBP*M337V)4Ptrc/J | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.