Table 2.
Human gene/locus | Detail | Human KI size | Technology | References |
---|---|---|---|---|
Whole gene humanisation | ||||
APOE | APO-E2, -E3, -E4 human variants (Alzheimer's and cardiovascular disease) | 4.1 kb | HR in ES cells | 39– 41 |
IL3, TPO, CSF1, CSF2, IL15, SIRPA | Supporting the human cellular component of chimaeric animals with a human immune system in immunodeficient mice | 8.5–17.5 kb | HR in ES cells | 44– 48 |
C5AR1 | To generate and study anti-human C5AR1 antibody efficacy (inflammation) | 1 kb | HR in ES cells | 49 |
PXR, CAR | Xenobiotic sensors; predicting human drug responses | 4.3 kb and 7 kb | HR in ES cells | 52, 53 |
GCGR | Humanising target of monoclonal antibody drug (diabetes) | 4.7 kb | HR in ES cells | 62 |
SIRPA and CYP2D6 | Testing ssODN-mediated end joining | 199.5 and 6.2 kb | ssODN-mediated end joining in rat zygotes | 124 |
KMT2D | Human cancer gene KI; testing CRISPR/Cas9-assisted HR in ES cells and homology arm lengths | 42 kb | CRISPR/Cas9-assisted HR in ES cells | 128 |
RHO | Whole Rhodopsin gene plus GFP tag (retinal degeneration) | 7.4 kb | Both HR and RMCE in ES cells | 106 |
Humanising large loci and gene clusters | ||||
IGH and IGK variable regions | Antibodies with human variable regions | 2.6 + 3 Mb | Iterative HR in ES cells | 56, 57 |
IGH, IGK, and IGL variable regions | Antibodies with human variable regions | 917 + 838 + 932 kb | S-RMCE in ES cells | 55 |
α globin cluster | Proof-of-principle for large humanisation and to study α globin gene expression | 117 kb | RMGR | 58 |
β globin genes | To study β thalassaemia | 8.7–11.7 kb | HR in ES cells | 94, 97– 99 |
CYP3A4/CYP3A7 | To study cytochrome P450-mediated drug metabolism | ~100 kb | RMCE in ES cells | 51 |
Transchromosomic mice | ||||
Chromosome 21 | Transchromosomic mouse model for Down syndrome | 42 Mb | MMCT | 54, 60, 61, 70, 71, 107 |
Immunoglobulin loci transchromosomic mice | Transchromosomic mouse model for human monoclonal antibody production | 1.5 + 2 Mb | MMCT | 102, 129 |
All mice are cited in the text