Lag3 Conditional Knockout mouse — T cell specific context
Lag3, the mouse ortholog of human LAG3, encodes a CD4 related type I membrane protein with four immunoglobulin superfamily domains, a distinctive extra loop in domain D1 that mediates high-affinity MHC class II binding, and additional reported ligands including fibrinogen like protein 1 and alpha-synuclein fibrils. Inhibitory output depends on the cytoplasmic FSAL motif and a glutamate proline repeat rather than classical ITIMs, and requires cis association with the T cell receptor complex, so LAG-3 dampens signaling by competing for peptide MHC class II and disrupting CD4 dependent assembly rather than by recruiting a canonical phosphatase. Alone, Lag3 nulls show mild phenotypes, but combined loss with Pdcd1 produces rapid lethal autoimmunity including myocarditis on permissive backgrounds, the genetic counterpart of relatlimab plus nivolumab synergy in melanoma. Choose humanization for antibody pharmacology because clinical reagents do not cross-react, and conditional deletion with Cd8-Cre when cell intrinsic exhaustion is the question.
Tissue restricted knockout of Lag3 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. For T cell work, plan Cre specificity, reporter crosses, and baseline phenotyping before you scale.
Catalog options
Conditional knockout focuses the experiment on t-cell 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 # | |
|---|---|---|---|---|---|
| Lag3-Flox | Conditional Knockout | KO/CKO mice | live | CKO 2105966 | Inquire |
Designing a Lag3 Conditional Knockout allele
Because germline nulls are viable and nearly silent, a floxed Lag3 allele earns its cost only when the question is compartmental. Flank the exons encoding D1 with its extra loop so recombination removes MHC class II binding rather than trimming the stalk. E8I-Cre restricts deletion to the CD8 lineage and is the right driver for cell-intrinsic exhaustion during chronic LCMV clone 13 or in tumors, though its recombination is frequently incomplete, so sort and PCR rather than trusting reported penetrance. Foxp3-Cre addresses the regulatory T cell arm, and Slc6a3-Cre suits questions about fibrillar alpha-synuclein uptake by dopaminergic neurons rather than immunology. With Cd4-CreERT2, dose tamoxifen before priming, since LAG-3 is induction dependent and late deletion leaves protein already at the synapse. Read out tetramer-positive CD8 numbers, interferon gamma and TNF co-production, TOX and TCF1 distribution, and viral or tumor burden.
Pricing and quotes
The Lag3 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 Lag3 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 Lag3 Conditional Knockout mouse models are available?
When Lag3 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 Lag3 knockout embryonic lethal in mice?
It depends on background and allele design. Some Lag3 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 t cell 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 t cell specific, so we start driver selection there.
Do you ship live Lag3 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 Lag3?
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.