Generation of an Obese Diabetic Mouse Model upon Conditional

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Loss of Atrx (alpha-thalassemia/mental retardation syndrome X-linked) is insufficient to cause pancreatic neuroendocrine tumors (PanNETs).
• Atrx plays a significant role in endocrine dysfunction.

Purpose of the Study:

• To characterize the Pdx1-Cre;AtrxKO (P.AtrxKO) genetically engineered mouse model (GEMM) for PanNET formation and endocrine disruption.
• To investigate the role of Atrx in metabolic homeostasis and pancreatic health.

Main Methods:

• Utilized Pdx1-Cre;AtrxKO GEMM, comparing knockout (P.AtrxHOM) to wild-type (P.AtrxWT) littermates.
• Monitored metabolic parameters including weight, hyperglycemia, and glucose intolerance over 24 months.
• Conducted histopathological analysis of pancreas and liver for fatty infiltration and steatosis.

Main Results:

• No PanNETs developed in P.AtrxKO mice.
• Both male and female P.AtrxHOM mice exhibited overweight/obesity, hyperglycemia, and glucose intolerance.
• Significant increase in pancreatic and peripancreatic fatty infiltration and hepatic macrovesicular steatosis observed in P.AtrxHOM mice.

Conclusions:

• Atrx deficiency in P.AtrxKO mice leads to obesity and diabetes but not PanNETs.
• This GEMM is a valuable tool for studying metabolic disorders and potentially for investigating additional oncogenic events.