Sexually-Dimorphic Effects in Cancer
While both girls and boys with NF1 are prone to develop optic gliomas, girls are more likely to experience visual decline from their tumors. Using genetically-engineered mice with optic gliomas, male and female mice both develop optic gliomas of the same size and growth rate; however, only female mice experience profound optic nerve dysfunction and visual loss. Similarly, whereas boys in the general population are much more likely to develop autism than girls, this sex ratio is blunted in children with NF1. We are currently exploring the possibility that female Nf1 mutant mice are more likely to exhibit behavioral deficits as a result of increased neuronal injury.
Current projects in the Gutmann research laboratory are focused on defining the molecular and cellular basis for the sexual dimorphism observed in optic nerve dysfunction in people and mice with NF1-associated optic glioma. Both gonadal sex hormone and epigenetic etiologies are being investigated. Similar studies are underway to determine the potential increased female vulnerability to behavioral deficits in the context of NF1.