| Popis: |
Phosphatase and Tensin Homolog (PTEN) acts as a key suppressor of the insulin signaling pathway and thus regulates cell growth and development (Leslie et al., 2008). In humans, this protein still has numerous clinically important variants of unknown significance (VUS) which are implicated in disorders such as autism spectrum disorder (ASD) and are classified as neither pathogenic nor benign (Yehia et al., 2020). Our research aims to classify five of these variants previously implicated in ASD using the model organism Caenorhabditis elegans (C. elegans) (Wong et al., 2019). The insulin pathway is well conserved across metazoans, and thus using this model organism is advantageous as this allows us to characterize PTEN variants by studying its C. elegans homolog DAF-18 (Post et al., 2020). In 2019, Wong et al. characterized DAF-18 variants D66E, L115V, H138R, H168Q, and T176I, which correspond to PTEN variants D22E, L70V, H93R, H123Q, and T131I implicated in ASD (Figure 1A-B). Their analysis focused on morphology and locomotion defects, while González-Cavazos et al. in 2019 studied the effects of these variants on dauer entry. Our work aimed not only to replicate the results found by González-Cavazos et al., 2019 but also to characterize the DAF-18 variants with three new assays: L1 arrest survival, Q-cell division in L1 arrest, and rate of pharyngeal pumping off-food. |
