Fig. 7
GRD domain is required for the tumor suppressor function of nf1 in MYCN-driven neuroblastoma tumorigenesis.
(A) Tumor penetrance of stable transgenic zebrafish with the genotypes of nf1a-/-;nf1b+/+;GFP;wt-GRD;mCherry (n = 31), nf1a-/-;nf1b+/+;GFP;mut-GRD;mCherry (n = 20) and nf1a-/-;nf1b+/+;GFP;mCherry (n = 41) at the age of 12 weeks. (B) nf1a-/-;nf1b+/+;MYCN;GFP fish injected with dbh:wt-GRD;dbh:mCherry (n = 58) showed a significantly lower mCherry+ mosaic tumor rate compared with the sibling fish injected with dbh:mut-GRD;dbh:mCherry (n = 25) at the age of 7 weeks (Fisher’s exact test), indicating the tumor suppression function of the NF1 GRD domain.Most early tumors arose in nf1a-/-;nf1b+/+;MYCN;GFP fish injected with dbh:wt-GRD; dbh:mCherry only expressed GFP (C) but not mCherry fluorescent protein (D). A significant subset of early tumors arose in nf1a-/-;nf1b+/+;MYCN;GFP fish injected with dbh:mut-GRD; dbh:mCherry did express both GFP (E) and mCherry (F).