Table 1.
Genetically modified pigs for use in biomedicine and agriculture.
| Use / Modification | Issue Addressed / Transgene Activity | Reference |
|---|---|---|
| Xenotransplantation | ||
| membrane cofactor protein, MCP (CD46) + | Hyperacute rejection: Complement Modifier | (Diamond et al., 2001) |
| human-decay accelerating factor, hDAF (CD55) + | Hyperacute rejection: Complement Modifier | (Langford et al., 1994) |
| CD59+ (MIRL) | Hyperacute rejection: Complement Modifier | (Fodor et al., 1994) |
| α-1,2-fucosyltransferase (FUT2) + | Hyperacute rejection: Carbohydrate remodeling | (Koike et al., 1996) |
| β-1,4- acetylglucosaminyltransferase (MGAT2) + * | Hyperacute rejection: Carbohydrate remodeling | (Miyagawa et al., 2001) |
| α-1,3-galactosyltransferase (GGTA1) −/− | Hyperacute rejection | (Lai et al., 2002a) |
| heme oxygenase I (HMOX1) + | Post-Hyperacute rejection | (Petersen et al., 2008a) |
| ecto-ATPase (CD39) + | Post-Hyperacute rejection | (Dwyer et al., 2007) |
| thrombomodulin (THBD) + | Post-Hyperacute rejection | (Petersen et al., 2007) |
| human leukocyte antigen, DP (HLA-DP) + | Cell Mediated rejection | (Tu et al., 1999) |
| human leukocyte antigen, DR (HLA-DR) + | Cell Mediated rejection | (Huang et al., 2006) |
| human leukocyte antigen, E (HLA-E) + / B2M + | Cell Mediated rejection | (Weiss et al., 2009) |
| tumor necrosis factor ligand superfamily, member 10 (TNFSF10) + | Cell Mediated rejection | (Klose et al., 2005) |
| tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) + | Cell Mediated rejection | (Oropeza et al., 2008) |
| Fas ligand (FASLG) + | Cell Mediated rejection | (Choi et al., 2010) |
| cytotoxic T lymphocyte-associated 4 (CTLA4) + | Non-Vascular rejection | (Martin et al., 2005) |
| Belatacept (LEA29Y) | Non-Vascular rejection | (Klymiuk et al., 2009) |
| porcine endogenous retroviruses (PERV) knock-down shRNA | Porcine Endogenous Retrovirus | (Dieckhoff et al., 2008) |
| Liver Transplantation | ||
| alpha-ferroprotein cytosine deaminase (AFP-CDA) + | Liver specific expression of cytosine deaminase | (Beschorner et al., 2003a) |
| albumin thymidine kinase 1 (ALB-TK1) + | Liver specific expression of thymidine kinase | (Beschorner et al., 2003b) |
| Liver Support | ||
| albumin (ALB) + | Artificial liver | (Naruse et al., 2005) |
| Immune Function | ||
| immunoglobulin kappa, constant region (IGKC) −/− | Delete light chain expression | (Ramsoondar et al., 2010) |
| immunoglobulin heavy chain, joining gene cluster (IGHJ) −/− | Delete antibodies and B cells | (Mendicino et al., 2010) |
| Disease Model | ||
| rhodopsin, mutant P347L (RHO P347L) + | Retinitis Pigmentosa | (Petters et al., 1997) |
| rhodopsin, mutant P23H (RHO P23H) + | Retinitis Pigmentosa | Ross et al. unpublished |
| cystic fibrosis transmembrane conductance regulator (CFTR) +/− and CFTRΔF508/+ |
Cystic Fibrosis | (Rogers et al., 2008) |
| Huntington (HTT) + | Huntington’s Disease | (Uchida et al., 2001) |
| omega 3 fatty acid desaturase + | Cardiovascular Disease | (Lai et al., 2006) |
| catalase (CAT)+ | Cardiovascular Disease | (Whyte et al., 2011b) |
| endothelial nitric oxide synthase 3 (NOS3) + | Cardiovascular Disease | (Whyte et al., 2010) |
| proprotein convertase, subtilisin/kexin-type, 9 (PCSK9) + | Familial Hypercholesterolemia | (Bolund et al., 2010) |
| apolipoprotein E (APOE) knock-down shRNA+ | Familial Hyperlipidemia | (El-Beirouthi et al., 2009) |
| gastric inhibitory polypeptide receptor, dominant negative (GIPR(dn)) + |
Diabetes | (Renner et al., 2010) |
| hepatocyte nuclear factor-1 homeobox A, dominant negative (HNF1A(dn)) + |
Diabetes | (Umeyama et al., 2009) |
| insulin 2, mutant C93S (INS2 C93S) + | Diabetes | (Renner et al., 2010) |
| amyloid precursor protein (APP) K670N+/M671L+ | Alzheimer's Disease | (Kragh et al., 2008) |
| mouse mammary tumor virus (MMTV)/v-Ha-ras + | Mammary Tumors | (Yamakawa et al., 1999) |
| survival motor neuron (SMN) +/− | Spinal Muscle Atrophy | (Lorson et al., 2011) |
| Pharmaceuticals | ||
| protein C (PROC) + | Protein C and anticoagulation | (Van Cott et al., 1997) |
| Factor VIII (FVIII) + | Human coagulation Factor VIII | (Paleyanda et al., 1997) |
| Factor IX (FIX) + | Human coagulation Factor IX | (Lindsay et al., 2004) |
| hemoglobin B, beta (HBB) + | Human hemoglobin beta | (Sharma et al., 1994) |
| colony-stimulating factor 2 (CSF2) + | Human granulocyte-macrophage colony-stimulating factor |
(Park et al., 2008) |
| Production Agriculture | ||
| growth hormone (GH) + | Growth hormone | (Hammer et al., 1985) |
| lactalbumin (bLALBA) + | Alpha-lactalbumin | (Bleck et al., 1998) |
| insulin-like growth factor 1 (IGF1) + | Increase muscle mass | (Pursel et al., 1999) |
| Sloan-Kettering viruses (c-Ski) + | Increase muscle mass | (Pursel et al., 1992) |
| phytase+ | Metabolize inorganic phosphorus | (Golovan, 2001) |
| delta 12 fatty acid desaturase+ | Spinach gene to change body composition | (Saeki et al., 2004) |
| heat-shock protein 70-KD protein 2 (HSPA2) + | Create animals resistant to heat stress | (Chen et al., 2005) |
| B-cell leukemia 2 (BCL2) + | Increase ovulation rate | (Guthrie et al., 2005) |
| myostatin pro-domain+ | Increase muscle mass | (Mitchell and Wall, 2008) |
| Tool Pig | ||
| enhanced green fluorescent protein (eGFP) + | Cell Tracking | (Cabot et al., 2001; Park et al., 2001) |
| enhanced blue fluorescent protein (eBFP) +, DsRed2 + | Cell Tracking | (Webster et al., 2005) |
| Kusabira-orange+ | Cell Tracking | (Matsunari et al., 2008) |
| tetracycline-inducible human-decay accelerating factor (TET-hDAF) +, tetracycline-inducible CD95 (TET-CD59) + |
Tetracycline dependent expression | (Kues et al., 2006) |
| octamer-binding transcription factor 4 (Oct4)-eGFP + | Germline-specific eGFP expression | (Nowak-Imialek et al., 2009) |
| β-galactosidase (LacZ) + | Cell Tracking | (Jackson et al., 2010) |
| eGFP- proteasome subunit, alpha-type, 1 (eGFP-PSMA1) + | Green labeling of proteasomes | (O’Gorman et al., 2010) |
| Technique Demonstration | ||
| knock out eGFP | KO of eGFP by zinc-finger nucleases | (Whyte et al., 2011a) |
| α-1,3-galactosyltransferase (GGTA1) −/− | KO of GGTA1 by using zinc-finger nucleases | (Hauschild et al., 2010) |
| phosphoglycerate kinase-eGFP (PGK-eGFP) + | Lental virus vectors | (Hofmann et al., 2003) |
| human-decay accelerating factor (hDAF) + | Sperm mediated gene transfer | (Lavitrano, 1997) |
| enhanced green fluorescent protein (eGFP)+ | Oocyte transduction | (Cabot et al., 2001) |
| cytomegalovirus enhancer/chicken beta-actin promoter∷Venus (CAGGS-Venus)+ | Sleeping beauty transposon-mediated transfection | (Garrels et al., 2010) |
| PiggyBac-mediated transposition | Tetracycline-dependent expression of RFP | (Kim et al., 2010) |
| retinoic acid 8-stimulated mitochondrial-localized enhanced yellow fluorescent protein (STRA8-mEYFP) | Retinoic acid inducible expression |
(Sommer et al., 2010) |
*
UDP-N-acetylglucosamine:alpha-6-D-mannoside-beta-1,2-N-acetylglucosaminyltransferase II