Targeted disruption of pancreatic-derived factor (PANDER, FAM3B) impairs pancreatic beta-cell function

a pancreatic islet-specific cytokine-like protein that is secreted from -cells upon glucose stimulation. The biological function of PANDER is unknown, and to address this we generated and characterized a PANDER knockout mouse. RESEARCH DESIGN AND METHODS—To generate the PANDER knockout mouse, the PANDER gene was disrupted and its expression was inhibited by homologous recombination via replacement of the first two exons, secretion signal peptide and transcriptional start site, with the neomycin gene. PANDER/ mice were then phenotyped by a number of in vitro and in vivo tests to evaluate potential effects on glucose regulation, insulin sensitivity, and -cell morphology and function. RESULTS—Glucose tolerance tests demonstrated significantly higher blood glucose levels in PANDER/ versus wild-type male mice. To identify the mechanism of the glucose intolerance