Fig 1.
NPcis derived sarcoma penetrance and tissue distribution.
a-c Pie chart representing the a percentage of mice developing sarcomas, b the sarcoma tissue sub-location and c the sarcoma body distribution. d Sarcoma incidence in relation to mouse sex. NPcis males [24/33 (72%)] develop more frequently sarcoma than NPcis females [10/15 (40%)]. e Representative H&E and S100, desmin and SMA immunohistological sarcoma characterization from NPcis mice in low (upper panels, scale bar equals to 5 mm) and high (bottom panels, scale bar equals to 100 μm) magnification.
Fig 2.
Histological characterization of dorsal root ganglion of NPcis mice.
a Venn diagram representing the low overlap between the NPcis mice that develop a sarcoma and the one that manifests NF clinical signs b low (upper, scale bar equals 500 μm) and high (bottom, scale bar equals 100 μm) magnification H&E of a normal dorsal root ganglion (left), an enlarged dorsal root ganglion (middle) of a NPcis mouse and an enlarged dorsal root ganglion (right) of a Hoxb7-Cre Nf1f/f mouse.
Table 1.
Neurofibroma-like clinical signs noticed in NPcis mice.
Fig 3.
Histological characterization of a plexiform neurofibroma arising in a peripheral nerve of a NPcis mouse.
a low magnification (scale bar equals to 2.5 mm) H&E of an enlarged peripheral nerve of a NPcis mouse b Histological characterization by H&E (left), immunostaining for S100 [middle (Schwann cells)] and toluidine blue [right (mast cells)]. Scale bar is equal to 100 μm.
Fig 4.
Histological characterization of a cutaneous neurofibroma arising in a NPcis mouse.
a Gross picture of a mouse developing a cNF b Gross picture depicting the cNF and its normal margin harvested for histological evaluation. c Histology of the normal margin skin of a NPcis mouse (left), skin lesion from a NPcis mouse (middle) and a skin lesion from a Hoxb7-Cre Nf1f/f mouse (right). Histological characterization by H&E (upper), immunostaining for S100 [middle (Schwann cells)] and toluidine blue [bottom (mast cells)]. Arrows point to the mast cells. Black scale bar is equal to 100 μm.
Fig 5.
10% of NPcis develop ear mass coinciding with earring tag.
a Picture of a NPcis mouse bearing an ear mass coinciding with the earring tag. b Ear mass incidence in relation to mice genotype. A fraction of NPcis mice [6 out of 58 (10%)] developed at least one ear mass but none of the 56 wild-type littermates did. c Representative H&E of an ear mass from one of the NPcis mouse. d Histological characterization by immunostaining for S100 (Schwann cells).
Fig 6.
Nerve injury in the sciatic nerves of NPcis mice induces the development of plexiform neurofibroma.
a Picture of a WT mouse 3 months post sciatic nerve injury by needle. b Histological characterization by H&E (left), immunostaining for S100 [left (Schwann cells)] and toluidine blue [right (mast cells)]. Arrows point to the mast cells. Black scale bar is equal to 100 μm. c Picture of a NPcis mouse 3 months post sciatic nerve injury by needle. d Histological characterization by H&E (left), immunostaining for S100 [left (Schwann cells)] and toluidine blue [right (mast cells)]. Black scale bar is equal to 100 μm. Malignant spindle cell proliferation with nuclear atypical and mitosis and/or necrosis distinguish sarcomas from plexiform neurofibroma. e Stacked histogram summarizing the percentage of normal, hypercellular, plexiform neurofibroma and MPNST in WT and NPcis following nerve injury by needle after 3 months in WT and NPcis mice. f Picture of a NPcis mouse submitted to surgery cutting the sciatic nerve at the sural, tibial and peroneal nerve ramification (sparing the sural nerve). g Stacked histogram summarizing the percentage of normal, hypercellular, pNF and MPNST in NPcis following nerve injury by needle or cut (at the sural, tibial and peroneal nerve ramification and sparing the sural nerve) after 1–6 months.
Fig 7.
NF1 and p53 expression in NPcis sciatic nerves injury-induced plexiform neurofibroma.
a Representative immunostaining for NF1 and p53 normal sciatic nerves (no injury) from wild-type mice, injury-induced sciatic nerves from NPcis mice that develop pNF, injury-induced sciatic nerves from NPcis mice that did not develop pNF and spontaneous sarcoma from NPcis mice. Scale bar is equal to 250 μm b Stacked histogram summarizing the percentage of tissues [normal sciatic nerves (no injury) from wild-type mice (n = 8), injury-induced sciatic nerves from NPcis mice that develop pNF (n = 12), injury-induced sciatic nerves from NPcis mice that did not develop (n = 9) pNF and spontaneous sarcoma from NPcis mice (n = 23)] categorized into different staining intensity level. c Bar graph representing the relative Nf1 (left) and p53 (right) gene expression level in normal sciatic nerves (no injury) from wild-type mice (n = 2), injury-induced sciatic nerves from NPcis mice that develop pNF (n = 2), injury-induced sciatic nerves from NPcis mice that did not develop (n = 2) pNF and spontaneous sarcoma from NPcis mice (n = 2).
Table 2.
Comparison between the sciatic nerve injury-induced NPcis mice and Nf1 tissue-specific knockout models.