Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9 -deficient mice

• Published in: Nature genetics Vol. 23; no. 1; pp. 71 - 75
• Main Authors: Kehrl, John H, Harrison, Kathleen A, Thaler, Joshua, Pfaff, Samuel L, Gu, Hua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.09.1999
• Subjects: Animals; Biological and medical sciences; Classical genetics, quantitative genetics, hybrids; DNA-Binding Proteins - metabolism; Eye Proteins; Forkhead Transcription Factors; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Glucagon - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Immunohistochemistry; Insulin - metabolism; Islets of Langerhans - abnormalities; Islets of Langerhans - embryology; Islets of Langerhans - metabolism; LIM-Homeodomain Proteins; Mice; Models, Genetic; Molecular Sequence Data; Motor Neurons - metabolism; Nerve Tissue Proteins; Paired Box Transcription Factors; Pancreas - abnormalities; Pancreas - embryology; Pancreas - metabolism; Pancreatic Polypeptide - metabolism; PAX6 Transcription Factor; Repressor Proteins; Somatostatin - metabolism; Time Factors; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Vertebrata; Immunohistochemistry; Embryonic development; Agenesis; Rodentia; Langerhans islet; Cell differentiation; Gene expression; Protein; Vertebrata; Mammalia; B-Cell; Mouse; Malformation; Homeotic gene; Mutation; Pancreas; Endocrine pancreas
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/12674

In most mammals the pancreas develops from the foregut endoderm as ventral and dorsal buds. These buds fuse and develop into a complex organ composed of endocrine, exocrine and ductal components. This developmental process depends upon an integrated network of transcription factors. Gene targeting experiments have revealed critical roles for Pdx1, Isl1, Pax4, Pax6 and Nkx2-2 (refs 3,4,5,6,7, 8,9,10). The homeobox gene HLXB9 (encoding HB9) is prominently expressed in adult human pancreas, although its role in pancreas development and function is unknown. To facilitate its study, we isolated the mouse HLXB9 orthologue, Hlxb9. During mouse development, the dorsal and ventral pancreatic buds and mature beta-cells in the islets of Langerhans express Hlxb9. In mice homologous for a null mutation of Hlxb9, the dorsal lobe of the pancreas fails to develop. The remnant Hlxb9-/- pancreas has small islets of Langerhans with reduced numbers of insulin-producing beta-cells. Hlxb9-/- beta-cells express low levels of the glucose transporter Glut2 and homeodomain factor Nkx 6-1. Thus, Hlxb9 is key to normal pancreas development and function.