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Rfx6 directs islet formation and insulin production in mice and humans.

Nature | 2010

Insulin from the beta-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor neurogenin 3 (Neurog3) initiates the differentiation of the beta-cells and other islet cell types from pancreatic endoderm, but the genetic program that subsequently completes this differentiation remains incompletely understood. Here we show that the transcription factor Rfx6 directs islet cell differentiation downstream of Neurog3. Mice lacking Rfx6 failed to generate any of the normal islet cell types except for pancreatic-polypeptide-producing cells. In human infants with a similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and subsequent sequencing identified mutations in the human RFX6 gene. These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate beta-cells for patients with diabetes.

Pubmed ID: 20148032 RIS Download

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: U19 DK061245-04
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK063720-045956
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK063720
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK021344
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK063720-05
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK063720-045957
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK063720-045958
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK063720-045954
  • Agency: NIDDK NIH HHS, United States
    Id: U19 DK061245
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK063720-045955
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK021344-26
  • Agency: NIDDK NIH HHS, United States
    Id: U19 DK061245-049001
  • Agency: CIHR, Canada

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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