Tardbp Conditional Knockout mouse models
Nuclear TDP-43, encoded by mouse Tardbp and orthologous to human TARDBP, is a heterogeneous nuclear ribonucleoprotein with two RRM domains binding UG-rich RNA and a C-terminal glycine-rich prion-like low complexity domain mediating phase separation and protein interaction. It represses cryptic exon inclusion in transcripts such as STMN2 and UNC13A, regulates splicing and mRNA stability, and autoregulates its own abundance by binding its 3-prime untranslated region. In ALS and frontotemporal lobar degeneration, TDP-43 mislocalizes from the nucleus and forms hyperphosphorylated, ubiquitinated cytoplasmic inclusions, and rare dominant mutations cluster in the low complexity domain, including M337V, A315T, and Q331K. Because Tardbp null embryos die around implantation and overexpression is independently toxic, endogenous locus knockins and conditional alleles are strongly preferred over transgenes. Match design to question, using nuclear localization signal mutants for mislocalization, patient missense knockins for aggregation, and humanized alleles when cryptic exon readouts require human sequence context.
Tissue restricted knockout of Tardbp keeps wild type function everywhere else. Breeding is often more robust, and the setup mirrors patient biology where mutations arise in a subset of cells.
What Tardbp Conditional Knockout mouse models are available?
ingenious targeting laboratory offers 1 distinct Tardbp (TDP43) conditional knockout catalog mouse model. Researchers can order pre-developed catalog lines or request a custom mouse model, including humanized, knockin, and transgenic variations with verified germline transmission.
Catalog table
| Model | Type | Category | Availability | Catalog # | Action |
|---|---|---|---|---|---|
| Tardbp-Flox | Conditional Knockout | KO/CKO mice, disease model mice | sperm cryopreservation | CKO 2102528 | Inquire |
Designing a Tardbp Conditional Knockout allele
Because germline nulls fail around implantation, a floxed allele is the only route to adult loss of function. Flank the exon carrying the initiator codon plus the second coding exon so that recombination removes both RRM domains and cannot yield an amino-terminally truncated product that still dimerizes. Choose drivers by circuit: Chat-Cre or Mnx1-Cre for spinal motor neurons, Camk2a-CreERT2 for forebrain excitatory neurons to model frontotemporal degeneration, Cx3cr1-CreER for microglial contribution, and Myf5 or Acta1 drivers if muscle-intrinsic effects are in question. Deletion is rapidly lethal to neurons, so tamoxifen dosing and time to harvest must be titrated rather than fixed. Autoregulation complicates mosaic tissue because unrecombined cells raise TDP-43 levels, which means quantification must be single-cell. Score nuclear TDP-43 loss by immunostaining, mouse-validated cryptic exon inclusion by RNA sequencing, neuromuscular junction denervation, and grip strength.
Conditional knockout focuses the experiment on your target tissue while the rest of the animal keeps a wild type allele. That pattern mirrors somatic mutation in patients and avoids systemic compensation that can erase subtle phenotypes. It is often preferred when a germline null is lethal, weak, or confounded by developmental rescue.
Pricing and quotes
The Tardbp Conditional Knockout lines listed above are catalog models. Send us the catalog number and our team confirms current availability, pricing, and whether the line ships cryopreserved or live.
If your study needs a Tardbp allele configuration that is not listed above, our scientific team designs and generates it. Model generation quotes return in about twenty four hours with project milestones and pricing.
FAQ
What Tardbp Conditional Knockout mouse models are available?
When Tardbp Conditional Knockout lines are in catalog, we ship from inventory. If your configuration is not listed, we design the allele to order. Common paths include conditional knockout, constitutive knockout, humanized, knockin, and transgenic options, with documented germline transmission and United States QC.
Is Tardbp knockout embryonic lethal in mice?
It depends on background and allele design. Some Tardbp germline knockouts are viable. Others need conditional alleles or mixed backgrounds. We review publications and our own experience, then recommend floxed versus null before you commit.
Which Cre driver is best for experiments?
Driver choice depends on onset timing, recombination efficiency, and known leak. We map your organ and cell type to a short list of proven Cre lines, then talk through reporter crosses and controls. We favor drivers with strong community validation for your tissue.
Do you ship live Tardbp animals?
When catalog lines are live, we ship with health certificates and QC documentation. If your exact combo is not listed, we quote a generation project with cryo or live dispatch depending on cohort timing and geography.
How do I request a quote for Tardbp?
Use the catalog inquire buttons or the request quote form. Include your allele goal, Cre plan if any, strain background, and cohort size. A PhD led team responds with pricing, milestones, and the fastest path to experimental animals.