Table 6 Genetically engineered models (GEM) used in meningioma research

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:

2–3 day neonates (PN-2–3) [27, 28, 30, 130], PN1 [31]

CC 360 [130], 450 [28], 117 [30], 339 [30]

SS 330 [27], 420 [27]

44% (24/55) [30], 30% (9/30) [27],

16% (4/25) [31], 12,5% (9/72) [28], 6% (1/18) [130]

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],

ND or 0% (0/43) [31, 130]

Histology [27, 28, 30, 31], IHC (PGDS) [28], MRI [28, 30], electron microscopy [28, 30], ND [130]

5 [27, 28, 30, 31, 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:

PN2 [30, 132]

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]

1[30, 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]

Gliomas 88% (23/26) [31], hydrocephalus 65% (17/26) [31]

Histology [31], IHC (PDGS) [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]

Gliomas 48% (14/29) [31], hydrocephalus 7% (2/29) [31]

Histology [31], IHC (PDGS) [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]

Histology [31], IHC (PDGS) [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]

–

Histology [133], IHC (Gli-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]

Histology [133], IHC [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]

Histology [134], IHC [134], RNA-seq [134], MRI [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]

Histology [134], IHC [134], RNA-seq [134], MRI [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]

Histology [134], IHC [134], RNA-seq [134], MRI [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]

Histology(1³¹⁾, IHC [131], electron microscopy [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]

Histology(1³¹⁾, IHC [131], electron microscopy [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]