Characterisation of an Atrx Conditional Knockout Mouse Model: Atrx Loss Causes Endocrine Dysfunction Rather Than Pancreatic Neuroendocrine Tumour.

ATRX is a chromatin remodeller that maintains telomere homeostasis. Loss of is described in approximately 10% of pancreatic neuroendocrine tumours (PanNETs) and associated with poorer prognostic features. Here, we present a genetically engineered mouse model (GEMM) addressing the role of loss () in pancreatic β cells, evaluating a large cohort of ageing mice (for up to 24 months (mo.)). loss did not cause PanNET formation but rather resulted in worsening of ageing-related pancreatic inflammation and endocrine dysfunction in the first year of life. Histopathological evaluation highlighted an exacerbated prevalence and intensity of pancreatic inflammation, ageing features, and hepatic steatosis in mice. Homozygous mice presented hyperglycaemia, increased weights, and glucose intolerance after 6 months, but alterations in insulinaemia were not detected. individuals presented an improper growth of their pancreatic endocrine fraction that may explain such an endocrine imbalance. A pilot study of BRACO-19 administration to mice resulted in telomere instability, reinforcing the involvement of in the maintenance of β cell telomere homeostasis. Thereby, a non-obese dysglycaemic GEMM of disrupted is here presented as potentially useful for metabolic studies and putative candidate for inserting additional tumourigenic genetic events.