Poster #078
Sex-dependent DNA Damage and Cell Death in Male, Smc3 Partial Loss Mice
Mentor: Sneha Varghese, Post-Doc
Diabetes results from dysfunction and loss of insulin-producing beta-cells, driven by metabolic stress and resulting accumulation of DNA damage. Beta-cells are vulnerable to DNA damage as they replicate rapidly after birth but later become non-dividing, making effective DNA repair essential. A key molecular complex that ensures healthy replication and DNA damage repair is the Cohesin complex (SMC3, SMC1, RAD21). Previously, our lab demonstrated that beta-cells of female mice with partial loss of SMC3 (Smc3 Hets) had increased DNA damage and reduced insulin production than wild-type mice. To determine if beta-cells from male mice are similarly susceptible to SMC3 deficiency, we are performing immunostaining for Insulin and DNA damage (ƔH2AX) on pancreatic sections from 11m Smc3Het and Control mice (n=6/group), TUNEL assay for apoptosis, fluorescent imaging, and morphometric quantification. Results could reveal sex-specific differences in Cohesin-mediated DNA damage control in beta-cells, enhancing our understanding of sex-dependent diabetes risk factors.