Tardbp Knockin 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.
Targeting Tardbp preserves positional context compared with viral or BAC approaches. That helps when you quantify expression or map chromatin.
What Tardbp Knockin mouse models are available?
ingenious targeting laboratory offers 1 distinct Tardbp (TDP43) knockin 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-M337V | Knockin | point mutantion mice, disease model mice | sperm cryopreservation | KI 232085 | Inquire |
Designing a Tardbp Knockin allele
Knockin at the endogenous locus is the preferred design for this gene because transgenic overexpression is toxic on its own and because the 3-prime untranslated region autoregulatory loop must stay intact for expression to remain physiological. Useful targets fall into three groups: low complexity domain missense changes of the M337V, A315T and Q331K class, which shift phase behavior and aggregation propensity; substitutions in the bipartite nuclear localization signal, which drive cytoplasmic accumulation and simultaneously relieve autoregulation, so watch total protein rise; and RRM1 lysine to glutamine acetylation mimics or carboxy-terminal serine to aspartate phospho-mimetics that test post-translational control of solubility. Introduce changes without leaving a selection cassette or a residual intronic FRT scar near splice sites. Interpret with fractionation into soluble and urea pools, phospho-TDP-43 immunostaining, nuclear to cytoplasmic ratio per cell, splicing changes by RNA sequencing, and motor endpoints.
Knockin and humanized formats keep regulatory context at the endogenous locus. For your target tissue focused programs, that matters when expression timing, splice isoforms, or allele dosage drive biology. Random integration transgenics can still help, but targeted alleles usually give cleaner pharmacology readouts.
Pricing and quotes
The Tardbp Knockin 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 Knockin mouse models are available?
When Tardbp Knockin 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.