This study investigates the role of the helicase-like transcription factor (HLTF) in pancreatic β cell function and survival. Researchers generated both global and β cell-specific Hltf Knockout (KO) mice in immune-competent (IC) and immune-deficient (ID) backgrounds. The β cell-specific Hltf KO mice were created by crossing Hltf^flox/flox mice with RIP-Cre transgenic mice, leading to the deletion of Hltf specifically in pancreatic β cells. In IC mice, β cell-specific Hltf deletion resulted in neonatal lethality due to increased DNA damage, activation of the Hmgb1-RAGE axis, and granzyme A-mediated β cell death. In contrast, ID mice lacking functional T, B, and NK cells survived, highlighting the role of the immune system in mediating β cell destruction upon Hltf deletion.
Deletion of Hltf in pancreatic β cells leads to DNA damage and activation of the Hmgb1-RAGE axis, resulting in granzyme A-mediated β cell death and neonatal lethality in immune-competent mice. The absence of this phenotype in immune-deficient mice underscores the immune system's role in this process.
Pancreatic β cell-specific Hltf conditional Knockout (CKO) mouse model, generated by crossing Hltf^flox/flox mice with RIP-Cre transgenic mice to achieve β cell-specific deletion of Hltf.
Type 1 diabetes, Pancreatic β cell apoptosis, DNA damage response, Immune-mediated β cell destruction
Conditional Knockout model, RIP-Cre driver, β cell-specific gene deletion, Immune-competent and immune-deficient mouse models
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
Certified health status from professional breeders
