Table 1.
Examples of partial and smaller scale genomically humanised mice created for different investigations
| Human gene/locus | Detail | Human KI size | Technology | References |
|---|---|---|---|---|
| Partial humanisation | ||||
| IGK constant region | Antibodies with human immunoglobulin kappa (light chain) constant regions | 0.5 kb | HR in ES cells | 126 |
| IGHG1 constant region | Antibodies with human immunoglobulin gamma-1 (heavy chain) constant regions | 2.1 kb | HR in ES cells | 127 |
| FOXP2 | Humanising 2 human-specific residues (related to human speech) | 2 bp | HR in ES cells | 13 |
| APP | Humanising 3 residues in Aβ domain plus human mutations (Alzheimer's disease) | 3–7 bp | HR in ES cells | 19– 21 |
| APOE | Humanising 1 residue critical to human APOE4 biochemistry (Alzheimer's and cardiovascular disease) | 1 bp | HR in ES cells | 26 |
| TP53 (p53) | Humanising core DNA-binding domain plus human mutations (cancer) | 2.8 kb | HR in ES cells | 30– 32 |
| BDNF | Modelling 2 human variant residues (psychiatric disorders) | 274 bp | HR in ES cells | 33 |
| OPRM1 | Humanising exon 1, with one of two human polymorphic variants (alcoholism) | 0.7 kb | HR in ES cells | 35 |
| AR | Humanising exon 1 including Q-tract expansions (spinal bulbar muscular atrophy) | 1.6 kb | HR in ES cells | 75, 81, 82 |
| HTT | Humanising exon 1 including Q-tract expansions (Huntington disease) | 250–500 bp | HR in ES cells | 83– 92 |
| TNFSF11 | Humanising single exon; target of monoclonal antibody drug (bone disorders) | 0.4 kb | HR in ES cells | 37 |
| FUS | Recapitulating FUS splice site mutation (‘delta14’), plus human frameshifted C-terminus (ALS) | 1 bp + 9 bp | HR in ES cells | 8 |
| IKAP | Humanising exon 20 + flanking introns, including human mutation (familial dysautonomia) | 1.5 kb | HR in ES cells | 38 |
| FKTN | Humanising exon 10 ± human-specific SVA retrotransposon insertion (Fukuyama muscular dystrophy) | 6 + 3 kb | RMCE in ES cells | 93 |
| PRNP | Humanising prion protein gene with mutation, minus signal peptide (prion diseases) | 0.8 kb | HR in ES cells | 103 |
| CTLA4 | Humanising gene minus signal peptide, to study anti-human CTLA4 antibody efficacy (cancer) | 3.2 kb | HR in ES cells | 104 |
| DMPK | Humanising exons 13–15 plus CTG repeats (myotonic dystrophy) | 1.5–1.7 kb | HR in ES cells | 105 |
| Humanising non-coding variants | ||||
| eQTL rs2277862; T | To model lipid-functional non-coding human variant | 5 bp | CRISPR/Cas9-assisted HR in zygotes | 122 |
All mice are cited in the text