daf-2 encodes the sole insulin / IGF-1-like receptor tyrosine kinase in C. elegans and sits at the head of the insulin/IGF signaling (IIS) cascade. When insulin-like peptides engage DAF-2, the receptor activates the PI3K AGE-1, generating PIP3 that recruits PDK-1 and AKT-1/2. AKT in turn phosphorylates the FOXO transcription factor DAF-16, retaining it in the cytoplasm and repressing longevity, stress-resistance, and dauer programs.
Reduced daf-2 signaling produces the most famous phenotype in aging biology: a roughly two-fold extension of adult lifespan together with enhanced oxidative, thermal, and pathogen stress resistance. Because the INSR/IGF1R → PI3K → AKT → FOXO axis is deeply conserved, daf-2 models speak directly to mammalian metabolic disease, cancer, and lifespan regulation. CD BioSciences designs and delivers custom daf-2 alleles — clean knockouts, kinase-domain point mutants, conditional or temperature-sensitive configurations, and fluorescent or epitope-tag knockins — with full genotype verification.
| Gene symbol | daf-2 (Insulin/IGF-1 receptor tyrosine kinase) |
|---|---|
| Protein product | DAF-2 — insulin / IGF-1 receptor (receptor tyrosine kinase) |
| Mammalian homolog | INSR / IGF1R (insulin receptor family) |
| Biological role | Receptor at the top of the C. elegans IIS cascade. Insulin-like peptide engagement activates DAF-2, which engages the PI3K AGE-1 and ultimately drives AKT-mediated phosphorylation and cytoplasmic retention of DAF-16/FOXO. |
| Loss-of-function phenotype | Reduced signaling gives constitutive dauer formation at 25 °C and roughly doubles adult lifespan, with strongly enhanced oxidative and thermal stress resistance. Null alleles are dauer-constitutive; partial loss-of-function alleles (e.g. e1370) give a clean, temperature-tunable longevity phenotype. |
| Why edit it | The founding longevity gene. daf-2 was the first single-gene mutation shown to double animal lifespan, and it established the IIS → PI3K → AKT → FOXO axis as a conserved controller of aging, metabolism, and developmental arrest. |
| Recommended background | N2 (wild type). Temperature-sensitive alleles are maintained at 15–20 °C and shifted as required; class-1 and class-2 alleles differ in dauer versus longevity bias. |
| Representative allele | e1370 (canonical temperature-sensitive reference allele); additional class-1 / class-2 alleles widely available. |
daf-2 at a glance: reduced signaling roughly doubles adult lifespan and confers strong stress resistance; the founding longevity gene. Editing daf-2 alone is a powerful way to dissect DAF-2 function in vivo, with conserved relevance to human INSR biology.
gRNA-guided Cas9 cutting with NHEJ repair to introduce frameshift indels, generating premature stop codons and null / strong-loss-of-function daf-2 alleles.
Homology-directed repair (HDR) inserts GFP / HA / FLAG or other tags at the daf-2 locus for endogenous expression and subcellular localization studies.
Introduce specific amino-acid substitutions to dissect functional domains and separate catalytic from scaffolding roles of DAF-2.
Build tissue-specific or inducible configurations and reporter lines for spatiotemporal analysis of DAF-2 function.
Define target (knockout / knockin / point mutation), select gRNA(s) and HDR template, confirm against the latest genome build.
Design, validate, and synthesize high-specificity guide RNAs targeting the daf-2 locus.
Build Cas9 / gRNA delivery construct and, for knockin, the homology-arm repair template.
Perform gonadal microinjection of N2 animals with CRISPR components and co-CRISPR selection markers.
PCR, Sanger / sequencing, and phenotype confirmation to isolate edited animals and verify alleles.
Provide homozygous / balanced daf-2 strains plus a full genotype and methods report.
Standard knockout projects deliver a frameshift indel allele predicted to produce a premature stop and a loss-of-function phenotype. We confirm the edit by sequencing and, where relevant, by characteristic phenotype assays.
Yes. Using HDR with a designed repair template, we can insert GFP, HA, or FLAG tags at the C- or N-terminus while preserving endogenous promoter and regulation.
Timelines vary with editing type and validation needs, but our optimized pipeline and co-CRISPR selection typically shorten turnaround versus conventional approaches. Contact us with your design for a project-specific estimate.
Complete loss of daf-2 drives constitutive dauer formation, which arrests development and complicates lifespan assays. Partial reduction-of-function alleles (notably e1370) and conditional configurations retain adult animals while still producing a robust, reproducible longevity phenotype. We will recommend the design that best fits your endpoint.
CD BioSciences is committed to convenient, efficient, and cost-effective C. elegans model customization. Tell us your target design — knockout, knockin, tagging, or point mutation — and our scientists will respond with a tailored plan and quote.
Contact UsReferences
1. Kim H. M., Colaiácovo M. P. CRISPR-Cas9-guided genome engineering in C. elegans. Current Protocols in Molecular Biology, 2016, 115(1): 31.7.1–31.7.18.
2. Kenyon C., Chang J., Gensch E., Rudner A., Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature, 1993, 366(6454): 461–464.
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