Fus Knockin mouse models
Fus encodes the FET family RNA-binding protein FUS, ortholog of human FUS, organized as an N-terminal QGSY-rich low complexity prion-like domain, an RGG-flanked RRM, a zinc finger, and a C-terminal PY nuclear localization signal recognized by Transportin-1; it binds nascent transcripts, regulates splicing and transcription elongation, and undergoes liquid-liquid phase separation that is normally restrained by nuclear import and arginine methylation. Amyotrophic lateral sclerosis mutations cluster in the PY-NLS, notably R521C and P525L, weakening Transportin binding and driving cytoplasmic mislocalization, stress granule partitioning and progressive aggregation, a toxic gain-of-function mechanism distinct from the nuclear loss seen in FTLD-FUS. Because constitutive nulls show perinatal lethality on C57BL/6 backgrounds and only partial recovery on outbred backgrounds, NLS-mutant knockins and Δ14 frameshift alleles are the designs that reproduce motor neuron degeneration at endogenous expression. Ewsr1 and Taf15 share domain architecture and buffer nuclear functions, so score cytoplasmic mislocalization directly.
An engineered Fus allele can introduce a human coding region, a point change, or a fluorescent reporter without random transgene integration noise.
What Fus Knockin mouse models are available?
ingenious targeting laboratory offers 2 distinct Fus knockin catalog mouse models. Researchers can order pre-developed catalog lines or request a custom mouse model, including humanized, knockin, and transgenic variations with verified germline transmission.
Designing a Fus Knockin allele
This is the design that reproduces motor neuron loss at endogenous expression. Target the PY nuclear localization signal, using the arginine and proline positions in mouse Fus that correspond to human R521 and P525 rather than assuming the human numbers apply, since the mouse protein is shorter and residue positions shift. Frameshift alleles that truncate the final exon and delete the signal outright give the most severe cytoplasmic redistribution and are usually studied as heterozygotes, because homozygotes are poorly viable. Arginine methylation in the adjacent RGG region tunes Transportin-1 binding, so methylation-site substitutions provide a graded series rather than an on or off allele. Avoid tags at the carboxy terminus, which sit inside the import signal. Endpoints that matter are nuclear to cytoplasmic FUS ratio per motor neuron, stress granule partitioning, insoluble fraction accumulation with age, neuromuscular junction denervation, and rotarod or grip decline against littermates.
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 Fus 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 Fus 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 Fus Knockin mouse models are available?
When Fus 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 Fus knockout embryonic lethal in mice?
It depends on background and allele design. Some Fus 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 Fus 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 Fus?
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.