We gene edit several different strains of mice, including C57BL/6, Balb/c, DBA2, and NOD-scid for use as disease models. Mouse model generation can use either CRISPR/CAS9 EGE™ or ESC-based gene editing technologies, for which the turnaround times are 6-8 months and 9-12 months, respectively. Mice are often the preferred mammalian model organisms due to their short life cycle and close genetic resemblance to humans. Particularly, humanized mouse models have great potential. Mice happen to be the best studied mammalian model organism with abundant genomic, transcriptomic, proteomic, and phenotypic collections.
- Strain: Laboratory mouse strains are either outbred or inbred. Outbred mice are usually bred to maintain maximum heterozygosity, whereas inbred mice are usually bred to maintain maximum homozygosity. Inbred strains (also called inbred lines) are particular species that have individual mice nearly identical to each other in genotype due to long inbreeding. A strain is inbred when it has undergone at least 20 generations of brother x sister or offspring x parent mating, at which point at least 98.6% of the loci in an individual of the strain will be homozygous, and each individual can be treated effectively as clones. C57BL/6(N and J), BALB/c, Fvb, A/J, C3H, CBA, DBA/2 etc. are inbred mouse strains.
- CRISPR/EGE™ or ESC/HR: At Biocytogen, 85% mouse and 100% rat gene editing projects are generated via EGE™ technology. Although EGE™ technology is comparatively cheaper and offers faster turnaround times compared to ESC-based projects, projects where the knockin size is greater than 15kb still necessitate the use of ESC/HR technology.
- Superovulation: Superovulation has been used in the production of transgenic mice since the late 1980s to artificially induce ovulation of large numbers of oocytes from limited numbers of female mice. Superovulation facilitates the generation of genetically engineered mice and reduces the number of animals used.
- Breeding: Breeding is one of the critical steps to generate genetically engineered mouse models. A suitable breeding environment is important to have large litter sizes and shorten the timelines to produce mouse models. Biocytogen’s AAALAC accredited SPF animal facilities provide optimal breeding environments. Our experts design the most efficient breeding scheme to save on costs and time for our customers.
CRISPR Knockin Mouse Application Example:
Humanized CD3ε Mouse Model Generation and Validation
Targeting Strategy
mRNA Expression Analysis
RT-PCR analysis of the B-hCD3ε gene: hCD3ε mRNA was detected in splenocytes isolated from homozygous B-hCD3ε mice.
Protein Expression Analysis
Splenocytes from both wild type (WT) C57BL/6 and homozygous B-hCD3ε mice were analyzed by flow cytometry.
Results: Mouse CD3+ cells were detectable in the WT C57BL/6 mice, whereas human CD3+ cells were detectable in the homozygous knockin mouse B-hCD3ε.
Other Genetically Modified Mouse Models
| Product | Product No | Application Fields |
|---|---|---|
| B-Apoe-KO Mice | B-EM-021 | Hyperlipidemia, atherosclerosis mice model (Cardiovascular system) |
| B-DTR-EGFP cKI Mice | 110151 | DTR conditional Knock-in mice model |
| B-F8 KO Mice | B-CM-007 | Hemophilia mice model |
| B-F9 KO Mice | B-CM-008 | Hemophilia mice model |
| B-Il17a-EGFP Mice | B-EM-017 | IL17 expression and functional test (gene reporter mice) |
| B-Il17a-Gluc Mice | B-EM-019 | IL17 expression and functional test (gene reporter mice) |
| B-PD-1-EGFP mice | 110166 | Functional study and mechanism of action study of PD-1 |
| B-db/db Mice | B-CM-012 | Diabetes mice model |
| B-ob/ob Mice | B-CM-059 | Diabetes mice model |
| B-p53 KO Mice | B-EM-020 | Tumorigenesis drug test |
| TGFb1-cKO Mice | B-EM-022 | Study on transforming growth factor |
Double Humanized Immune-checkpoint Mice
Triple Humanized
| Product | Product No | Background |
|---|---|---|
| B-hPD-1/hPD-L1/hCD40 mice | 131083 | C57BL/6 |
| B-hPD-1/hPD-L1/hCTLA4 mice | 130571 | C57BL/6 |
| B-hPD-1/hPD-L1/hTIGIT mice | 130573 | C57BL/6 |
| B-hPD-1/hPD-L1/hTNFR2 mice | 130849 | C57BL/6 |
| B-hPD1/hLAG3/hTIM3 mice | 130999 | C57BL/6 |
Single Humanized Immune-checkpoint Mice
| Product | Product No | Background | |
|---|---|---|---|
| B-hB7-H3 mice | 110028 | C57BL/6 | |
| B-hBTLA mice | 110005 | C57BL/6 | |
| B-hCCR8 mice | 110096 | C57BL/6 | |
| B-hCD27 mice | 110006 | C57BL/6 | |
| B-hCD28 mice | 110007 | C57BL/6 | |
| B-hCD38 mice | 110046 | C57BL/6 | |
| B-hCD3E mice | 110008 | C57BL/6 | |
| B-hCD40 mice | 110009 | C57BL/6 | |
| B-hCD47 (C) mice | 110615 | BALB/c | |
| B-hCD47 mice | 110010 | C57BL/6 | |
| B-hCD73 mice plus | 110047 | C57BL/6 | |
| B-hCTLA4 mice | 110011 | C57BL/6 | |
| B-hHAVCR2 (TIM3) mice | 110018 | C57BL/6 | |
| B-hLAG3 mice | 110013 | C57BL/6 | |
| B-hOX40L mice | 110043 | C57BL/6 | |
| B-hPD-1 mice | 110003 | C57BL/6 | |
| B-hPD-1 mice Plus | 110019 | C57BL/6 | |
| B-hPD-L1 (CD274) mice | 110015 | C57BL/6 | |
| B-hSIRPα mice | 110016 | C57BL/6 | |
| B-hTIGIT mice | 110017 | C57BL/6 | |
| B-hTNFRSF18 (GITR) mice | 110012 | C57BL/6 | |
| B-hTNFRSF4 (OX40) mice | 110014 | C57BL/6 | |
| B-hTNFRSF9 (4-1BB) mice | 110004 | C57BL/6 |
Humanized Immune-Checkpoint Mice
| Product | Product No | Background |
|---|---|---|
| B-hA2AR mice | 110120 | C57BL/6 |
Humanized Cytokines Mice
| Product | Product No | Background |
|---|---|---|
| B-hIL10 mice | 110060 | C57BL/6 |
| B-hIL1B mice | 110075 | C57BL/6 |
| B-hIL1RAcP mice | 110072 | C57BL/6 |
| B-hIL2 mice | 110085 | C57BL/6 |
| B-hIL23A/hIL12B mice | 120553 | C57BL/6 |
| B-hIL2RA mice | 110066 | C57BL/6 |
| B-hIL33 mice | C57BL/6 | |
| B-hIL4 mice | 110051 | C57BL/6 |
| B-hIL4/IL4RA mice | 120551 | C57BL/6 |
| B-hIL4RA Mice | 110052 | C57BL/6 |
| B-hIL6/hIL6R mice | 120550 | C57BL/6 |
| B-hTNFA mice | 110002 | C57BL/6 |
Cre Mouse Models List
| Product | Product No | Application Fields |
|---|---|---|
| B-ALB-CreERT2 Mice | 110137 | Alb promoter-driven inducible Cre mouse model (liver) |
| B-CAG-iCreERT2 mice | 110147 | Cre ubiquitous expression in mice |
| B-CAG-tdTomato cKI Mice | 110148 | Cre-induced tdTomato expression, for Cre expression profile detection |
| B-CD150-iCreERT2 Mice | 110142 | CD150 promoter-driven inducible Cre mouse model (Thymic, T cells and macrophages) |
| B-Cam1(Mcpt5)-iCre mice | 110138 | |
| B-Cdh5-iCreERT2 mice | 110140 | Cdh5 promoter-driven inducible Cre mouse model ( lung adult, subcutaneous fat pad adult) |
| B-Col10a1-iCre Mice | 110122 | Col10a1 promoter-driven Cre mouse model (mature hypertrophic chondrocyte) |
| B-Col2a1-iCre Mice | 110123 | Col2 promoter-driven Cre mouse model (type II collencyte) |
| B-Dcp2-iCreERT2 mice | 110138 | Dcp2 promoter-driven inducible Cre mouse model. (Macrophages) |
| B-Dmp1-iCre Mice | 110124 | Dmp1 promoter-driven Cre mouse model (skeleton) |
| B-Gfap-iCre mice | 110155 | Gfappromoter-driven Cre mouse model. (Astroglia) |
| B-Grpr-iCre Mice | 110125 | Grpr promoter-driven Cre mouse model (digestive system, nervous system) |
| B-Ins1-iCreERT2 Mice | 110126 | Ins1 promoter-driven inducible Cre mouse model (pancreas isletbeta cell) |
| B-Myh6-iCreERT2 mice | 110127 | Myh6 promoter-driven inducible Cre mouse model (Heart) |
| B-Ncr1 (Nkp46)-iCre Mice | 110127 | Ncr1 promoter-driven Cre mouse model (NK cell) |
| B-Oxr1-iCreERT2 Mice | 110128 | Oxr1 promoter-driven inducible Cre mouse model (frontal lobe adult, cerebellum adult and 24 other tissues) |
| B-Pdgfrb-iCre Mice | 110129 | Pdgfrb promoter-driven inducible Cre mouse model (parietal cell of multiple organs, such as skin, intestinal tract, kidney, lung and plexus vasculosus around central nervous system) |
| B-Prrx1-iCre Mice | 110130 | Prrx1 promoter-driven Cre mouse model (mesenchyme) |
| B-Sp7 (Osx)-iCre Mice | 110131 | Sp7 promoter-driven Cre mouse model (skeleton) |
| B-Syn1-iCre Mice | B-CM-005 | Syn1promoter-driven inducible Cre mouse model (brain) |
| B-Tcf21-iCreERT2 mice | 110141 | Tcf21 promoter-driven inducible Cre mouse model (bladder, lung) |
| B-Tex264-iCre-EGFP mice | 110136 | Tex264 promoter-driven Cre mouse model（Ubiquitous expression in adrenal,kidney and 28 other tissues） |
| B-Tnfrsf11a (RANK)-iCre Mice | B-EM-009 | Tnfrsf11a promoter-driven Cre mouse model (lymph gland formation and osteoclast differentiation system) |
| B-Ucp1-iCre Mice | 110134 | UCP1 promoter-driven Cre mouse model (mitochondria, brown fat) |
| B-Zeb1-iCreERT2 Mice | 110135 | Zeb1 promoter-driven inducible Cre mouse model (tunica media of artery and myocardial cell) |
B-NDG-Based Mouse Models
| Product | Product No | Background |
|---|---|---|
| B-NDG B2m KO mice plus | 110601 | B-NDG |
| B-NDG HLA-A2.1 mice | 110599 | B-NDG |
| B-NDG hIL15 mice | 110600 | B-NDG |
| B-NDG hTHPO mice | 110590 | B-NDG |
B-NDG Background Mouse Models
| Product | Product No | Background |
|---|---|---|
| B-NDG KitW-v mice | 110588 | B-NDG |
| B-NDG hSIRPA mice | 110003 | B-NDG |
Humanized Cytokines Mice
| Product | Product No | Background |
|---|---|---|
| B-hIL17A Mice | 110053 | C57BL/6 |
Other Humanized Mice
| Product | Product No | Background |
|---|---|---|
| B-hCCR2 mice | 110097 | C57BL/6 |
| B-hFcRn mice | 110001 | C57BL/6 |
| B-hTLR9 mice | 110103 | C57BL/6 |
Tetra Humanized Immune-checkpoint Mice
| Product | Product No | Background |
|---|---|---|
| B-hPD-1/hPD-L1/hSIRPA/hCD47 mice | 140577 | C57BL/6 |
Triple Humanized Immune-checkpoint Mice
| Product | Product No | Background |
|---|---|---|
| B-hPD-1/hPD-L1/h4-1BB mice | 130569 | C57BL/6 |
| B-hPD-1/hPD-L1/hCTLA4 mice | 130571 | C57BL/6 |
| B-hPD-1/hPD-L1/hLAG3(plus) mice | 130572 | C57BL/6 |
| B-hPD-1/hPD-L1/hTIM3 mice | 130574 | C57BL/6 |
| B-hPD-1/hSIRPA/hCD47 mice | 130562 | C57BL/6 |
| B-hPD-L1/hSIRPA/hCD47 mice | 130561 | C57BL/6 |
| Product | Product No | Background |
|---|---|---|
| B-HLA-A2.1 Mice | 110110 | C57BL/6 |
| B-hC5AR1 Mice | 110078 | C57BL/6 |
| B-hCCR4 mice | 110098 | C57BL/6 |
| B-hCD226 mice | 110869 | C57BL/6 |
| B-hCD39 mice | 110792 | C57BL/6 |
| B-hCD73 mice | 110027 | C57BL/6 |
| B-hCD94 Mice | 110044 | C57BL/6 |
| B-hCSF1R mice | 110035 | C57BL/6 |
| B-hETAR mice | 110108 | C57BL/6 |
| B-hIL13 mice | 110058 | C57BL/6 |
| B-hIL2RB mice | 110737 | C57BL/6 |
| B-hIL2RG mice | 110087 | C57BL/6 |
| B-hLAG3 mice plus | 110025 | C57BL/6 |
| B-hNKG2A mice | 110041 | C57BL/6 |
| B-hTLR8 Mice | 110104 | C57BL/6 |
| B-hTNFA/hIL17A mice | 120548 | C57BL/6 |
| B-hTNFA/hTNFR2 mice | 120749 | C57BL/6 |
| B-hTNFR2 mice | 110032 | C57BL/6 |
