The humanized TFRC mouse model is developed by Knockin at the mouse TFRC locus, and expresses a chimeric protein with a human extracellular domain (ECD) and a murine transmembrane and intracellular domain.
The humanized TFRC mouse model was intercrossed with the hSA/FcRn double humanized mouse model to enable translatable PK and biodistribution of compounds targeting TFRC.
Expression of TFRC (anti-mouse TFRC clone C2, anti-human TFRC clone OKT-9) on TER-119+ cells from freshly isolated bone marrow cells (A), blood (B), and splenocytes (C), gated on single viable cells.
Splenocytes of hTFRC mice were incubated with human conjugate pHrodo red transferrin for 2 hours at 37°C. Internalization of human transferrin (Tf) was confirmed by the increase of the MFI values of pHrodo Tf.
Specific activity of hTFRC: pre-incubation of splenocytes with pHrodo competitor, rh-transferrin, reduced the level of pHrodo internalization.
Combination of anti-hTFRC/anti-BACE1, but not anti-BACE1 alone, enables the biodistribution of IgG in the brain and the reduction of amyloid-β.
Rational: anti-BACE1 inhibits amyloid-b(Ab) production in vivo (Atwal et al.,2011)
hTFRC mice were treated with different anti-BACE1/anti-TFRC antibodies for 24h. Concentrations of hIgG and Ab were quantified by ELISA-based assay in plasma and brain homogenates.
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