Table 2.

Examples of whole gene and larger-scale genomically humanised mice created for different investigations

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