TMIC-106. Gene expression of olfactomedin-like 3, a potent protumorigenic molecule, is tightly regulated across post-natal development in male and female C57Bl/6 mice

Glioblastoma (GBM), a common primary brain tumor in adults, is uniformly fatal. The median survival time of 15 months has not changed in decades, highlighting the critical need for novel therapeutic approaches. Recent work from our laboratory, and others, have implicated a robust pro-tumorigenic role for olfactomedin-like 3 (OLFML3). We have shown that mRNA levels of OLFML3 is negatively correlated with survival in GBM patient samples. Moreover, we have shown that OLFML3 promotes tumor cell invasion and a pro-tumorigenic microglial phenotype. Our recent work has identified that OLFML3 is a critical protein for development and may be sexually dimorphic, which may have implications for its role in GBM development and progression. To further explore differences in Olfml3 gene expression across post-natal development and sex, this work aimed to quantify Olfml3 mRNA levels in cortical brain tissue from female and male mice at several developmental timepoints. Relative gene expression was assessed at 2, 4, 6, 8, 16, and 24 weeks of age using quantitative real-time PCR (RT-qPCR). My results showed that Olfml3 expression was stable across post-natal development and adulthood and did not differ across sex. Moreover, Olfml3 mRNA levels were similar between wild-type and Olfml3 heterozygote mice (two-way repeated measures ANOVA with posthoc Tukey’s test; p > 0.05), suggesting that Olfml3 expression is tightly regulated, potentially through compensatory mechanisms. This foundational work will pave the way for future studies to investigate these regulatory pathways and their possible role in GBM development and/or progression.