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PMID:15680365
Citation |
Lee, CS, Sund, NJ, Behr, R, Herrera, PL and Kaestner, KH (2005) Foxa2 is required for the differentiation of pancreatic alpha-cells. Dev. Biol. 278:484-95 |
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Abstract |
The differentiation of insulin-producing beta-cells has been investigated in great detail; however, little is known about the factors that delineate the second-most abundant endocrine lineage, the glucagon-producing alpha-cell. Here we utilize a novel YAC-based Foxa3Cre transgene to delete the winged helix transcription factor Foxa2 (formerly HNF-3beta) in the pancreatic primordium during midgestation. The resulting Foxa2(loxP/loxP); Foxa3Cre mice are severely hypoglycemic and die within the first week of life. Mutant mice are hypoglucagonemic secondary to a 90% reduction of glucagon expression. While the number of mature glucagon-positive alpha-cells is dramatically reduced, specification of alpha-cell progenitors is not affected by Foxa2 deficiency. By marker gene analysis, we show that the expression of the alpha-cell transcription factors Arx, Pax6, and Brn4 does not require Foxa2 in the transcriptional hierarchy governing alpha-cell differentiation. |
Links |
PubMed Online version:10.1016/j.ydbio.2004.10.012 |
Keywords |
Animals; Base Sequence; Cell Differentiation; Chromosomes, Artificial, Yeast; DNA Primers; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; Embryonic Development/genetics; Gene Deletion; Gene Expression Regulation, Developmental; Genotype; Hepatocyte Nuclear Factor 3-beta; Hypoglycemia/genetics; Islets of Langerhans/embryology; Mice; Mice, Knockout; Nuclear Proteins/deficiency; Nuclear Proteins/genetics; Pancreas/embryology; Reproducibility of Results; Transcription Factors/deficiency; Transcription Factors/genetics |
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Significance
Annotations
Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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See also
References
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