From: Meningioma animal models: a systematic review and meta-analysis
Genetically Engineered Models | ||||||||
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Genetic lesion (mice) | Method of gaining lesion | Activation | Duration of incubation | Tumor Take Rate % (pooled animals) | Type of meningioma | Tumor take non-meningiomas/other pathological findings | Validation/verification | # |
Nf2(flox2/flox2) | Conditional knockout. AdCre injection 3μl (3 × 108 pfu) [27, 31, 130], (5 × 1010–1 × 1011 pfu) [30] subdural frontally [27, 30, 130] and transorbitally [27] | Injection: | Transitional [27, 28], meningothelial [27, 28, 30, 31], fibroblastic [27, 28, 30, 31], psammomatous [28] —benign [27, 28, 31], Grade 1 [30], ND [130] | SCH 10% (3/30) [27], osteoma 51% (80/157) [27, 28, 30], liver tumor 17% (26/157) [27, 28, 30], osteosarcoma 3% (1/30) [27], hydrocephalus 34% (61/182) [27, 28, 30, 31], | Histology [27, 28, 30, 31], IHC (PGDS) [28], MRI [28, 30], electron microscopy [28, 30], ND [130] | |||
Ptprj(−/−) | Ptprj(−/−) mice [130] | – | CC 360 [130] | 0% (0/6) [130] | – | 0% (0/6) [130] | – | 1 [130] |
Ptprj(−/−); Nf2(flox2/flox2) | Conditional knockout AdCre injection 3 μl (3 × 108 pfu) subdural frontally [130] | Injection: PN2-3 [130] | CC 360 [130] | 25% (11/44) [130] | ‘Typical meningioma’ whorls and psammoma bodies – Benign in appearance [130] | 0% (0/44) [130] | Histology [130] IHC (Merlin, absent in Nf2 neg tumors) [130] | 1 [130] |
Nf2(flox2/flox2); p53(±) | Conditional knockout AdCre injection 3 μl (3 × 108 pfu) subdural frontally [27] and transorbitally [27] | Injection: PN2-3 [27] | SS 165 [27] | 12% (4/33) [27] | Transitional, meningothelial, fibroblastic—benign [27] | MPNST 3% (1/33) [27], SCH 3% (1/33) [27], osteoma 64% (21/33) [27], sarcoma 85% (28/33) [27], osteosarcoma 6% (2/33) [27], liver tumor 12% (4/33) [27], pituitary adenoma 3% (1/33) [27], hydrocephalus 45% (15/33) [27] | Histology [27] | 1 [27] |
Nf2(flox2/flox2); p16(ink4a)(−/−) | Conditional knockout AdCre injection 3 μl (3 × 108 pfu) subdural frontally [28] and transorbitally [28] | Injection: PN2 [28] | CC 450 [28] | 37% (10/27) [28] | Meningothelial [28], transitional [28], psammomatous [28] or fibroblastic [28]—Benign [28] 2/10 atypical features (prominent nucleoli, crowded cells) [28] | Osteoma 78% (21/27) [28], Liver tumor 19% (5/27) [28], hydrocephalus 56% (15/27) [28] | Histology [28], IHC (PGDS) [28], MRI [28], electron microscopy [28] | 1 [28] |
Nf2(flox2/flox2);ink4ab(−/−) (p16(ink4a)(−/−); p15(ink4b)(−/−); p19(arf)(flox2/flox2)) | Conditional knockout AdCre injection 3 μl (5 × 1010–1 × 1011 pfu) subdural [30, 132] | Injection: | CC 90 [132] SS 105 [30] | 85% (17/20) [132] 72% (38/53) [30] | 66% (25/38) Grade 1 [30] 32% (12/38) Grade 2 [30] 3% (1/38) Grade 3 [30] Fibroblastic and meningothelial [30] 11/17 meningothelial [132], 5/17 transitional [132], 1/17 fibroblastic [132] | Osteomas 23% (12/53) [30], liver tumor 79% (42/53) [30], subcutaneous sarcoma 34% (18/53) [30], hydrocephalus 32% (17/53) [30], ND [132] | Histology [30, 132], IHC [30], MRI [30], electron microscopy [30, 132], BLI [30], confocal microscopy [132] | |
Nf2(flox2/flox2);ink4ab(−/+) (p16(ink4a)(−/+); p15(ink4b)(−/+); p19(arf)(flox2/+)) | Conditional knockout AdCre injection 3 μl (5 × 1010–1 × 1011 pfu) subdural [30] | Injection: PN2 [30] | SS 234 [30] | 50% (28/56) [30] | 75% (21/28) Grade 1 [30] 14% (4/28) Grade 2 [30] 11% (3/28) Grade 3 [30] Fibroblastic and meningothelial [30] | Osteomas 32% (18/56) [30], liver tumor 59% (33/56) [30], subcutaneous sarcoma 9% (5/56) [30], hydrocephalus 46% (26/56) [30] | Histology [30], IHC [30], MRI [30], electron microscopy [30] | 1 [30] |
Nf2(flox2/−); p16(ink4a)(−/+) | Conditional knockout Knock-in approach PDGS + leptomeninges cells. PDGS(Cre) [29] | PDGScre (meningeal PGDS + cells) E12.5-PN2 [29] | SS 16/24 survived 15 months [29] | 50% (8/16) [29] | 6/16 meningothelial, 6/16 fibroblastic (4 with concomitant tumors)—benign [29] | Osteoma 81% (13/16) [29], pituitary tumor 69% (11/16) [29], hydrocephalus 13% (2/16) [29] | Histology [29], IHC [29], electron microscopy [29] gene expression profile [29] | 1 [29] |
Nf2(flox2/−); p16(ink4a)(−/−) | Conditional knockout Knock-in approach PDGS + leptomeninges cells. PDGS(Cre) [29] | PDGScre (meningeal PGDS + cells) E12.5-PN2 [29] | SS 16/22 survived 15 months [29] | 81% (13/16) [29] | 8/16 meningothelial, 8/16 fibroblastic (3 with concomitant tumors)—benign [29] | Osteoma 88% (14/16) [29], pituitary tumor 6% (1/16) [29], hydrocephalus 31% (5/16) [29] | Histology [29], IHC [29], electron microscopy [29], gene expression profile [29] | 1 [29] |
Nf2(flox2/−); p53(flox/−) | Conditional knockout Knock-in approach PDGS + leptomeninges cells. PDGS(Cre) [29] | PDGScre (meningeal PGDS + cells) E12.5-PN2 [29] | SS 135 [29] | 43% (6/14) [29] | Fibroblastic—benign [29] | MPNST 29% (4/14) [29], osteosarcoma 79% (11/14) [29], pituitary tumor 14% (2/14) [29], choroid plexus tumor 29% (4/14) [29] | Histology [29], IHC [29], electron microscopy [29], gene expression profile [29] | 1 [29] |
PDGF-B | Conditional knockout PGDS tv-a induced via 4 μl/2 × 105 RCAS-producing DF-1 cells subdurally [31] | RCAS/tv-a system alone Injection: PN3 [31] | SS 240 [31] | 26% (7/27) [31] | Benign meningiomas [31] | 1 [31] | ||
PDGF-B;Nf2(flox/flox) | Conditional knockout PGDStv-a (PDGF-B) (as described above) AdCre (Nf2(flox/flox)) (as described above) [31] | Injection: PN1: AdCre [31] PN3: RCAS [31] | SS 189 [31] | 52% (15/29) [31] | 60% (9/15) Grade 1 [31], 40% (6/15) Grade 2 [31] | 1 [31] | ||
PDGF-B; Nf2(flox/flox);Cdkn2ab(−/−) | PGDStv-a (PDGF-B) AdCre (Nf2(flox/flox); Cdkn2ab(−/−)) [31] | Injection: PN1: AdCre [31] PN3: RCAS [31] | SS 54 [31] | 79% (15/19) [31] | 33% (5/15) Grade 1 [31] 47% (7/15) Grade 2 [31] 20% (2/15) Grade 3 [31] | Gliomas 79% (15/19) [31] | 1 [31] | |
SmoM2 (Rosa26-lox-STOP-lox-SmoM2) | Conditional knockout PDGSCre;SmoM2 [133] | PDGScre (meningeal PGDS + cells) E12.5 [133] | SS 426 [133] | 21% (9/42) [133] | All meningothelial, grade 1 [133] | – | 1 [133] | |
SmoM2 (Rosa26-lox-STOP-lox-SmoM2) | Conditional knockout AdCre;SmoM2 [133] | Injection: PN2 [133] | SS 84 [133] | 2% (1/53) [133] | 1/1 Meningothelial, Grade 1 [133] | Medulloblastoma 8% (4/53) [133] | 1 [133] | |
YAP1-MAML2-V1 Nestin/tv-a Cdkn2a null mice | RCAS/tva-system. Injection of 1 × 105 DF1 cells in 1 ul volume [134] | Deep Injection: PN1-3 [134] | ND(134) | 42% (5/12) [134] | Meningioma-like tumors [134] 1/12 extra-axial, 2/12 intraventricular, 2/12 extra-cranial | ND [134] | 1 [134] | |
YAP1-MAML2-V2 Nestin/tv-a Cdkn2a null mice | See above Conditional activation of lesion Double activation RCAS/tva-system [134] | Deep and superficial Injection: PN1-3 [134] | 67–164 [134], 80–150 [134] | 43% (3/7) (deep) [134] 68% (13/19) (superficial) [134] | Meningioma-like tumors [134] Deep: 1/7 extra-axial, 2/7 intraventricular, Superficial: 5/19 extra-axial, 6/19 intraventricular, 6/19 extra-cranial | ND [134] | 1 [134] | |
NLS-2SA-YAP1 Nestin/tv-a Cdkn2a null mice | See above Conditional activation of YAP1 Single activation RCAS/tva-system [134] | Superficial Injection: PN1-3 | 80–123 [134] | 97% (29/30) [134] | Meningioma-like tumors.[134] 17/29 extra-axial, 25/29 intraventricular, 25/29 extra-cranial | ND [134] | 1 [134] | |
p16(−/−);p19(−/−) | Injection ENU dose (carcinogen) 25 mg/kg body weight [131] | Injection: Gestation age 14 (E14) [131] | SS: 98–133 [131] | 5% (2/43)a [131] | Non-invasive benign [131] | b7/8 tumor bearing mice had multiple alveola-bronchiolar adenomas [131] | 1 [131] | |
p16(±);p19(±) | Injection ENU dose (carcinogen) 25 mg/kg body weight [131] | Injection: E14 [131] | SS: 210–273 [131] | 33% (6/18)a [131] | Non-invasive benign [131] | b7/8 tumor bearing mice had multiple alveola-bronchiolar adenomas [131] | 1 [131] | |
p16(+/+);p19(+/+) | Injection ENU dose (carcinogen) 25 mg/kg body weight [131] | Injection: E14 [131] | ND [131] | 0% (0/24) [131] | – | – | – | 1 [131] |