Htt Conditional Knockout mouse — neural specific context
Huntington disease work centers on Htt, the mouse ortholog of human HTT, encoding huntingtin, a 350 kDa HEAT-repeat scaffold that organizes vesicular and axonal transport along microtubules through HAP1 and the dynein/dynactin machinery, sustains BDNF transcription by sequestering REST in the cytoplasm, and supports selective autophagy cargo recognition and ciliogenesis. Pathology follows CAG repeat expansion in exon 1 beyond roughly 36 units, generating an elongated polyglutamine tract that drives aggregation, aberrant exon 1 splicing into a highly toxic fragment, and somatic repeat instability in striatal medium spiny neurons through MSH3 and mismatch repair activity. Because complete Htt loss is embryonic lethal near gastrulation, conditional floxed alleles are mandatory for adult loss-of-function and lowering-safety studies, whereas full-length or humanized exon 1 CAG knockins preserve endogenous regulation for instability and biomarker endpoints far better than randomly integrated transgenes. Align allele class with endpoint, pairing neuron-restricted or striatum-restricted Cre drivers with region-specific silencing questions.
A floxed Htt allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ. For neural work, plan Cre specificity, reporter crosses, and baseline phenotyping before you scale.
Catalog options
Conditional knockout focuses the experiment on neuron 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.
| Model | Type | Category | Availability | Catalog # | |
|---|---|---|---|---|---|
| Htt-Flox | Conditional Knockout | KO/CKO mice | sperm cryopreservation | CKO 2100397 | Inquire |
Designing a Htt Conditional Knockout allele
There is no substitute, since homozygous null embryos fail before somitogenesis. Two distinct experiments justify the allele. Deletion after development tests whether huntingtin is required for maintenance, the direct surrogate for non-selective lowering safety; excising a floxed exon 1 from an expanded knockin instead tests reversibility of established pathology. Match driver to region: Drd1-Cre and Adora2a-Cre separate direct and indirect pathway medium spiny neurons, Emx1-Cre or CaMKIIalpha-Cre cover cortex, Slc6a3-CreERT2 addresses dopaminergic input, and Alb-Cre answers hepatic safety. Nestin-Cre gives broad but mosaic embryonic deletion, and high Cre expression is itself toxic to striatal neurons, so include Cre-only controls. Score DARPP-32 and enkephalin in striatum, brain-derived neurotrophic factor transcript, cytoplasmic versus nuclear REST, autophagy markers, clasping and rotarod, and verify excision in sorted nuclei.
Pricing and quotes
The Htt 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 Htt allele configuration that is not listed above, our scientific team designs and generates it. Model generation quotes return in about twenty four hours with milestones for genotyping, QC, and dispatch.
FAQ
What Htt Conditional Knockout mouse models are available?
When Htt 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 Htt knockout embryonic lethal in mice?
It depends on background and allele design. Some Htt 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 neuron specific focused 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. Your note points to neuron specific, so we start driver selection there.
Do you ship live Htt 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 Htt?
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.