Table 3.
Global and tissue-specific IGF1 transgenic and IGF1(R) KO mouse lines
| Mouse lines | Discovery (year/lab/first) | Expression control | Serum GH | Serum IGF1 | Size / weight | Body composition | Insulin sensitivity | Reproductive capacity | Cancer incidence | Lifespan | Original references | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Global | IGF1 | 1988 Palmiter (Mathews) | Mt1 + human IGFI cDNA | ↓ | ↑ | ↑ weight | n/a | n/a | – | n/a | n/a | [257] |
| IGF2+/− | 1990 Robertson (DeChiara) | NeoR replacing exon 2 of Igf2 | n/a | n/a | ↓ | n/a | n/a | – | n/a | n/a | [259] | |
| IGF1-/- | 1993 Efstratiadis (Liu) | deleting exon 4 of Igf1 | n/a | ↓ | ↓ | n/a | n/a | n/a | n/a | neonatal lethality; ↓ | [260] | |
| IGF1R-/- | 1993 Efstratiadis (Liu) | deleting exon 3 of Igf1r | n/a | n/a | ↓ | n/a | n/a | n/a | n/a | complete neonatal lethality | [260] | |
| Liver | TTR-IGF-1 | 2006 Xu (Liao) | transthyretin | ↓ | ↑ | ↑ | ↑ lean | ↑ glucose tolerance | – | – | n/a | [263] |
| HIT |
2009 LeRoith (Wu) |
transthyretin | – | ↑ | ↑;↑L,K,S | ↓fat | – | – | n/a | n/a | [265] | |
| KO-HIT |
2009 LeRoith (Wu) |
transthyretin + IGF1 null | – | ↑ | ↓at birth; – at 16 wk | ↓fat | – | –♂;↓♀ | n/a | No prenatal lethailty | [265] | |
| GHRKO-HIT | 2013 Yakar (Wu) | transthyretin | n/a | – | ↓; ↓K,S,H | ↓ muscle; ↑brown AT | – | n/a | n/a | n/a | [267] | |
| LID | 1999 LeRoith (Yakar) | albumin/Cre | ↑ | ↓ | – | – | ↓ | – | ↓ | ↑ ♀ | [268] | |
| LI-IGF1-/- |
1999 Ohlsson (Sjögren) |
Mx/Cre induced at ~ 1 mo | ↑ | ↓ | –; ↓K, ↑L at 3mo; ↓ wight at 13 mo | ↓ femur length at 3 mo; ↓ fat at 13 mo | ↓ | – | n/a | ↑ mean lifespan ♀ | [270] | |
| Adipose | IGF-1RaP2Cre | 2008 Blüher (Kloting) | aP2/Cre | – | ↑ | ↑ | ↑ fat | – | n/a | n/a | n/a | [273] |
| F-IGFRKO | 2016 Kahn (Boucher) | Adipo/Cre | n/a | ↑ | – | ↓ fat | – | n/a | n/a | n/a | [277] | |
| Brain | bIGF1RKO+/− | 2008 Holzenberger (Kappeler) | nestin/Cre | ↓ | ↓ | ↓ | ↑ fat | ↓ | infertile (-/-) | ↓ | ↑ mean lifespan (+/−); – (-/-) | [278] |
| Muscle | Skeletal Muscle IGF1 | 1995 Schwartz (Coleman) | avian skeletal α-actin driving human IGF1 | n/a | – | – | ↑ superficial gluteus muscle mass | n/a | n/a | n/a | n/a | [279] |
| MKR | 2001 LeRoith (Fernandez) | MCK + dominant-negative IGF1R | n/a | n/a | ↓ weight | n/a | ↓ | n/a | n/a | n/a | [280] | |
| MIGIRKO | 2015 Kahn (O'Neil) | ACTA1/Cre | n/a | n/a | ↓ | ↓ muscle | – | n/a | n/a | ↓ | [281] | |
| M-IGF1R KO | 2016 Kahn (O'Neil) | ACTA1/Cre | n/a | n/a | – | – | n/a | n/a | n/a | ↓ | [281, 282] | |
| Cardiac | IGF1 | 1996 Anversa (Reiss) | α-MHC + human IGF1 | n/a | ↑ | – at birth, ↑ on day 210; ↑ organ weights | – | n/a | ↓ using both Tg mice as breeders | n/a | – | [283] |
| Cardiomyocyte IGF-1 | 2007 Rosenthal (Santini) | α-MHC + rat mIGF1 | n/a | n/a | n/a | n/a | n/a | Hets as breeders | n/a | n/a | [284] | |
| CIGF1RKO | 2008 Abel (Kim) | Myosin 6/Cre | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | [285] | |
| iCMIGF-IRKO | 2012 Gödecke (Moellendorf) | 4-OHTX inducible Myosin 6/Cre at 3&11 mo | n/a | ↑ | ↓ size in newborns | n/a | – | n/a | n/a | n/a | [286] | |
| Endothelial | hIGFREO | 2012 Kearney (Imrie) | TIE2 + hIGF1R | n/a | n/a | – | n/a | – | n/a | n/a | n/a | [287] |
| EC IGF-1RKO | 2011 Kearney (Abbas) | TIE2/Cre, male 3–5 mo | n/a | n/a | n/a | n/a | – | n/a | n/a | n/a | [288] | |
| Endothelial IGF-1RKO | 2015 Cheng (Liang) | VE-Cadherin/Cre, male 3–4 mo | n/a | n/a | – | n/a | n/a | – | n/a | n/a | [289] | |
| Myeloid (Macrophage) | MIKO | 2016 Dixit (Spadaro) | LysM/Cre | n/a | n/a | n/a | ↑ fat | ↓ on HFD | n/a | n/a | ↑ pro-longevity effects | [290] |
| MΦ-IGF1RKO | 2016 Delafontaine (Higashi) | LysM/Cre x IGF1R/APOE-/- FLOX | n/a | n/a | n/a | n/a | n/a | n/a | n/a | n/a | [292] | |
| Bone | OC-IGF-1 Tg | 2000 Clemens (Zhao) | osteocalcin + rat IGF1 | n/a | – | – | n/a | n/a | n/a | n/a | n/a | [293] |
| Osteoblast IGF1 Tg | 2006 Kream (Jiang) | rat Col1a1 + murine Igf1 | n/a | ↑ | ↑ weight ♂ | n/a | n/a | n/a | n/a | n/a | [294] | |
|
Osteoblast IGF1R KO |
2002 Clemens (Zhang) | osteocalcin/Cre | n/a | n/a | – | n/a | n/a | n/a | n/a | n/a | [296] | |
| OBIGF1R−/− | 2015 Bikle (Wang) | Col1α1/Cre | n/a | n/a | – | n/a | n/a | n/a | n/a | n/a | [298] | |
| Chondrocyte IGF1 KO | 2007 Mohan (Govoni) | Col2α1/Cre | n/a | – | ↓ length | ↓ bone size, weight | n/a | n/a | n/a | n/a | [299] | |
| Osteocyte IGF1 KO | 2013 Lau (Sheng) | Dmp-1/Cre | n/a | – | n/a | ↓ femur length | n/a | n/a | n/a | n/a | [301] | |
| DMP-IGF-1R KO | 2016 Yakar (Liu) | DMP-1/Cre | ↑ at 8 wk; – at 16 wk | – | – | n/a | n/a | n/a | n/a | n/a | [224] | |
| Ovarian granulosa cells | IGF1Rgcko | 2017 Stocco (Baumgarten) | ESR2 + CYp19 | n/a | n/a | n/a | n/a | – | infertile | n/a | n/a | [303] |
| Pancreatic beta cells | β cell IGF-1R KO |
2002 Efstratiadis (Xuan); Kahn (Kulkarni) |
rat insulin/Cre | n/a | n/a | n/a | n/a | glucose intolerant; ↓ insulin secretion | n/a | n/a | n/a | [304, 305] |
| Steroidogenic cells | Steroidogenic cells IGF-1R KO | 2018 Nef (Neirijnck) | human P450SCC/Cre | n/a | n/a | – | ↓ testicular weight | n/a | – | n/a | n/a | [307] |
| Somatotroph | SIGFRKO | 2010 Radovick (Romero) | rGHpCre | ↑ | ↑ | ↓ weight;—length; ↑ L, S | ↓ fat | – | n/a | n/a | n/a | [308] |
| Thyrocyte | Thyrocyte specific IGF-1R KO | 2011 Krohn (Muller) | thyroglobulin/Cre | n/a | – | ↑weight in males; ↓ in females | alteration in perigonadal fat mass | ↑ males | n/a | n/a | n/a | [310] |
“—” indicates no change; n/a indicates not available. “wk” indicates weeks of age, “mo” indicates months of age. “Tg” indicates transgenic mice. “ +/− “ indicates heterozygous; “-/- “ indicates homozygous. ♂ indicates males; ♀ indicates females; K, kidney, L, liver, S, spleen, H, heart.