• CD98, also known as 4F2, is a widely expressed disulfide-linked heterodimer in the solute transporter family. It consists of an 85 kDa glycosylated type II transmembrane heavy chain and a 40‑50 kDa non-glycosylated light chain with 12 transmembrane segments. It is expressed on T, B, NK cells, granulocytes and many cell lines. The multifunctional protein CD98 heavy chain (CD98HC, Slc3a2) associates with integrin b1 through its cytoplasmic and transmembrane domains and the CD98HC-mediated integrin signaling is required for maintenance of ES cell proliferation.
• CD98hc is significantly abundant in the capillaries and microvessels of the mouse brain, localizing to both the luminal and abluminal surfaces of brain endothelial cells. It heterodimerizes with one of six CD98 light chains to form amino acid transporters that can transport a total of 15 different amino acids across the blood-brain barrier (BBB), including both small and large neutral amino acids, as well as cationic amino acids.
• The exons 2-10 of rat Cd98 gene that encode the extracellular domain were replaced by human CD98 exons 4-12 in B-hCD98HC rats.
• Human CD98HC was exclusively detectable on T cells and B cells in homozygous B-hCD98HC rats.
• This product is used for tumor pharmacology and safety evaluation of anti-CD98HC antibody, as well as assessing the potential of the drug to penetrate the blood-brain barrier.

Gene targeting strategy for B-hCD98HC rats. The exons 2-10 of rat Cd98 gene that encode the extracellular domain were replaced by human CD98 exons 4-12 in B-hCD98HC rats.

Strain specific analysis of CD98HC mRNA expression in SD rats and B-hCD98HC rats by RT-PCR. Kidney and brain RNA were isolated from SD rats (+/+) and homozygous B-hCD98HC rats (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with rat or human CD98HC primers. Rat Cd98hc mRNA was detectable only in SD rats. Human CD98HC mRNA was detectable only in homozygous B-hCD98HC rats but not in SD rats.

Strain specific CD98HC expression analysis in wild-type SD rats and homozygous humanized B-hCD98HC rats by flow cytometry. Splenocytes were collected from wild-type SD rats (+/+) and homozygous B-hCD98HC rats (H/H) (female, 7-week-old, n=1). Protein expression was analyzed with anti-rat CD98HC antibody (Biolegend, 206404) and anti-human CD98HC antibody (BD, 556077) by flow cytometry. Rat CD98HC was only detectable in wild-type SD rats. Human CD98HC was exclusively detectable in homozygous B-hCD98HC rats, but not in wild-type SD rats.