Ldlr Knockin mouse models
Ldlr, the mouse ortholog of human LDLR, encodes the cell surface receptor that clears apoB-containing lipoproteins, built from seven class A cysteine-rich ligand-binding repeats, EGF-A and EGF-B modules flanking a beta-propeller that mediates acid-dependent ligand release, an O-linked sugar domain, and a cytoplasmic NPXY motif read by Ldlrap1 for clathrin-mediated internalization; Pcsk9 binding to EGF-A diverts the receptor to lysosomal degradation instead of recycling, and Mylip ubiquitination provides a sterol-responsive degradation route. Loss-of-function alleles cause familial hypercholesterolemia, and null mice are viable but develop hypercholesterolemia and atherosclerosis on Western diet, making them a standard cardiovascular platform. Allele choice follows the question: a null for plaque biology, patient point mutations for class-specific trafficking defects, and full humanization when the endpoint is PCSK9 antibody efficacy, siRNA silencing, or base editing of the human sequence. Combining with Apoe or Apobec1 alleles tunes lipoprotein profiles toward human-like distributions.
Knockin designs at Ldlr support head to head comparisons between wild type and modified alleles because regulatory DNA stays in place.
What Ldlr Knockin mouse models are available?
ingenious targeting laboratory offers 1 distinct Ldlr 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 |
|---|---|---|---|---|---|
| Ldlr-C223R | Knockin | point mutantion mice | embryo cryopreservation | KI 00043 | Inquire |
Designing a Ldlr Knockin allele
Knockins earn their place here because familial hypercholesterolemia is mechanistically stratified, and only a point mutation preserves the distinction. Transport-defective substitutions in the cysteine-rich repeats or the beta-propeller trap the receptor in the endoplasmic reticulum, binding-defective changes in repeats four and five leave a mature surface protein that cannot hold apoB, and mutation of the tyrosine in the cytoplasmic NPXY motif blocks Ldlrap1 recruitment while surface expression and ligand binding stay intact. Introduce the human substitution at the orthologous mouse codon only after confirming residue conservation, and keep heterozygotes, since receptor dosage is the clinically relevant state. Separate the classes experimentally: endoglycosidase H sensitivity and pulse-chase for maturation arrest, surface biotinylation for delivery, four degree binding versus thirty-seven degree internalization of labeled LDL for uptake, and acid-wash recycling assays for release failure, then anchor all of it to plasma cholesterol.
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 Ldlr 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 Ldlr 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 Ldlr Knockin mouse models are available?
When Ldlr 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 Ldlr knockout embryonic lethal in mice?
It depends on background and allele design. Some Ldlr 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 Ldlr 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 Ldlr?
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.