Genetically engineered pigs manifesting pancreatic agenesis with severe diabetes.

INTRODUCTION

Pancreatic duodenum homeobox 1 () expression is crucial for pancreatic organogenesis and is a key regulator of insulin gene expression. Hairy and enhancer of split 1 () controls tissue morphogenesis by maintaining undifferentiated cells. encodes a basic helix loop helix (bHLH) transcriptional repressor and functionally antagonizes positive bHLH genes, such as the endocrine determination gene neurogenin-3. Here, we generated a new pig model for diabetes by genetic engineering and genes.

RESEARCH DESIGN AND METHODS

A transgenic (Tg) chimera pig with germ cells carrying a construct expressing under the control of the promoter was used to mate with wild-type gilts to obtain Tg piglets.

RESULTS

The Tg pigs showed perinatal death; however, this phenotype could be rescued by insulin treatment. The duodenal and splenic lobes of the Tg pigs were slender and did not fully develop, whereas the connective lobe was absent. β cells were not detected, even in the adult pancreas, although other endocrine cells were detected, and exocrine cells functioned normally. The pigs showed no irregularities in any organs, except diabetes-associated pathological alterations, such as retinopathy and renal damage.

CONCLUSION

Tg pigs were an attractive model for the analysis of pancreatic development and testing of novel treatment strategies for diabetes.