2001
DOI: 10.1101/gad.901601
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Tissue-specific deletion of Foxa2 in pancreatic β cells results in hyperinsulinemic hypoglycemia

Abstract: We have used conditional gene ablation to uncover a dramatic and unpredicted role for the winged-helix transcription factor Foxa2 (formerly HNF-3␤) in pancreatic ␤-cell differentiation and metabolism. Mice that lack Foxa2 specifically in ␤ cells (Foxa2 [Key Words: Hepatocyte nuclear factor; persistent hyperinsulinemic hypoglycemia of infancy; familial hyperinsulinism]

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Cited by 178 publications
(167 citation statements)
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“…However, the ␣-cells in doubleheterozygous mutant mice appeared to be functional (no differences in plasma glucagon levels were observed in mice of various genotypes) and present at the same relative ratio to ␤-cells as in Wt. As a change in islet morphology has also been noted in Nkx2.2, Nkx6.1, and Hnf-3␤-deficient mice (4,24,25), the reduced expression levels of these genes in Pdx-1 ϩ/Ϫ ͞Hnf-3␤ ϩ/Ϫ and Pdx-1 ϩ/Ϫ ͞Hnf-1␣ ϩ/Ϫ mice may therefore contribute to this phenotype. In addition, the double heterozygous mice had reduced expression of E-cadherin.…”
Section: Discussionmentioning
confidence: 99%
“…However, the ␣-cells in doubleheterozygous mutant mice appeared to be functional (no differences in plasma glucagon levels were observed in mice of various genotypes) and present at the same relative ratio to ␤-cells as in Wt. As a change in islet morphology has also been noted in Nkx2.2, Nkx6.1, and Hnf-3␤-deficient mice (4,24,25), the reduced expression levels of these genes in Pdx-1 ϩ/Ϫ ͞Hnf-3␤ ϩ/Ϫ and Pdx-1 ϩ/Ϫ ͞Hnf-1␣ ϩ/Ϫ mice may therefore contribute to this phenotype. In addition, the double heterozygous mice had reduced expression of E-cadherin.…”
Section: Discussionmentioning
confidence: 99%
“…Briefly, total pancreatic insulin concentration was determined (n=4 mice per genotype) using the above-described kit after acid-ethanol extraction [37]. Pancreatic beta cell mass was determined by immunostaining of paraffin-embedded pancreatic sections (n=3 mice× three slides per genotype) [38] with a guinea pig polyclonal antibody against mouse insulin (Zymed, San Francisco, CA, USA). Immunostaining of pancreatic GPX1 protein (n =3 mice×three slides per genotype) was conducted using a rabbit polyclonal antibody against bovine GPX1 (Lab Frontier, Seoul, Korea).…”
Section: Methodsmentioning
confidence: 99%
“…Mutant mice with specific ablation of Foxa2 in fetal b-cells have disorganized islet architecture and dysregulated insulin secretion as a consequence of reduction in the expression of K ATP channel, Kir6.2, and sulfonylurea receptor 1 (SUR1)]. The resultant neonatal Foxa2 mutants die shortly after birth from severe hyperinsulinemic hypoglycemia (Sund et al, 2001). These findings on the Foxa2 requirement in fetal endocrine cells were added to by recent studies indicating that Foxa2/Foxa1 maintain the normal physiological status of the mature pancreas.…”
Section: Class Iii: Maturation Factorsmentioning
confidence: 99%