• EGFR is expressed in various tissues. Upon binding of ligands like EGF to the EGFR receptor, EGFR dimers are formed. The activation of EGFR dimers stimulates intracellular tyrosine kinases, resulting in phosphorylation that triggers downstream signaling cascades, leading to cancer cell proliferation and the proliferation of new blood vessels within cancer cells. The mechanism of action of EGFR-targeting drugs primarily involves blocking or inhibiting the activity of EGFR, thereby preventing the growth and spread of cancer cells.
• A chimeric CDS that encodes human EGFR extracellular domain, rats EGFR signal peptide, transmembrane and cytoplasmic domain, followed by rats 3’UTR-STOP is inserted right after rats Egfr exon2. The chimeric EGFR protein expression will be driven by endogenous rats Egfr promoter, while rats Egfr gene transcription and translation will be disrupted.
• Rats Egfr mRNA was only detectable in wild-type SD rats. Human EGFR mRNA was exclusively detectable in homozygous B-hEGFR rats but not in wild-type SD rats. Human EGFR was detectable in heart, liver, esophagus, skin and ovary of B-hEGFR rats.
• This product is used for tumor pharmacology and safety evaluation of anti-human EGFR antibodies.

Gene targeting strategy for B-hEGFR rats. A chimeric CDS that encodes human EGFR extracellular domain, rats EGFR signal peptide, transmembrane and cytoplasmic domain, followed by rats 3’UTR-STOP is inserted right after rats Egfr exon2. The chimeric EGFR protein expression will be driven by endogenous rats Egfr promoter, while rats Egfr gene transcription and translation will be disrupted.

Strain specific analysis of EGFR mRNA expression in wild-type SD rats and B-hEGFR rats by RT-PCR. Liver RNA were isolated from wild-type SD rats (+/+) and homozygous B-hEGFR rats (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with rats or human EGFR primers. Rats Egfr mRNA was only detectable in wild-type SD rats. Human EGFR mRNA was exclusively detectable in homozygous B-hEGFR rats but not in wild-type SD rats.

Immunohistochemical (IHC) analysis of EGFR expression in homozygous B-hEGFR rats. The heart, liver, spleen, esophagus, skin and ovary were collected from wild-type rats and homozygous B-hEGFR rats (H/H) (female, 8-week-old, n=1), analyzed by IHC with anti-EGFR (Invitrogen, MA5-49312). Human EGFR was detectable in heart, liver, esophagus, skin and ovary of B-hEGFR rats. The arrow indicates tissue cells with positive EGFR staining (brown). “+” indicates that the tissue is positive, and “-” indicates that the tissue is negative.