CRISPR/Cas9-mediated humanization of mouse IgG1 Fc domain in hFCGRT transgenic mice

Validation Score: 0.900 Price: $0.50 B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr transgenic mice Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting IGHG1 in B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr transgenic mice. Primary outcome: Production of human IgG1 Fc-mouse IgG Fab2 chimeric antibodies

Description

This experiment involved using CRISPR/Cas9-mediated homology-directed repair to replace the mouse immunoglobulin heavy constant gamma 1 (IGHG1) Fc domain with the human IGHG1 Fc domain in hFCGRT transgenic mice (Tg32 strain). The goal was to create mice that produce human IgG1 Fc-mouse IgG Fab2 chimeric antibodies at physiologically relevant levels to better model human competitive conditions for IgG-based biologics. The engineered mice were designed to provide endogenous human IgG competition that more accurately reflects human physiology, addressing a recognized limitation of existing FcRn-humanized mouse models that lack endogenous human IgG.

TARGET GENE
IGHG1
MODEL SYSTEM
B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr transgenic mice
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
FcRn-mediated IgG recycling pathway
SOURCE
extracted_from_pmid_33025844
PRIMARY OUTCOME
Production of human IgG1 Fc-mouse IgG Fab2 chimeric antibodies

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.900 composite

📖 Wiki Pages

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Protocol

CRISPR/Cas9-mediated homology-directed repair to replace mouse IGHG1 Fc domain with human IGHG1 Fc domain in hFCGRT transgenic mice

Expected Outcomes

Mice producing physiologically relevant levels of human IgG1 Fc-containing chimeric antibodies that can compete with administered humanized mAbs

Success Criteria

Production of chimeric IgG1 at physiologically relevant levels and demonstration of competitive effects on humanized mAb pharmacokinetics

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