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


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 components1,2. 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 pancreas11, 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 β-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 β-cells. Hlxb9–/– β-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.

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Figure 1: Hb9 in the islets of Langerhans of adult mice.
Figure 2: Hb9 is expressed in the developing pancreas.
Figure 3: The dorsal lobe of the pancreas fails to develop in Hlxb9–/– mice.
Figure 4: Expression of Pdx1, Isl1, Pax6 and Hnf3β in Hlxb9–/– mice.
Figure 5: Abnormal islets of Langerhans in Hlxb9–/– mice.

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We thank M. Rust for excellent editorial assistance, A. Walsh for performing the blastocyte injection and A.S. Fauci for continued support.

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Correspondence to John H. Kehrl.

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Harrison, K., Thaler, J., Pfaff, S. et al. Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Nat Genet 23, 71–75 (1999).

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