PAX6 mutation alters circadian rhythm and β cell function in mice without affecting glucose tolerance.

Autor: Chhabra NF; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Amarie OV; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany., Wu M; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Amend AL; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Rubey M; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Gradinger D; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Irmler M; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany., Beckers J; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Chair of Experimental Genetics, Center of Life and Food Sciences, Weihenstephan, Technische Universität München, Freising, Germany., Rathkolb B; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Ludwig-Maximilians-Universität München, Gene Center, Chair for Molecular Animal Breeding and Biotechnology, Munich, Germany., Wolf E; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Ludwig-Maximilians-Universität München, Gene Center, Chair for Molecular Animal Breeding and Biotechnology, Munich, Germany., Feuchtinger A; Helmholtz Zentrum München, Research Unit Analytical Pathology, Neuherberg, Germany., Huypens P; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Teperino R; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Rozman J; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Przemeck GKH; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Hrabě de Angelis M; Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany. hrabe@helmholtz-muenchen.de.; German Center for Diabetes Research (DZD), Neuherberg, Germany. hrabe@helmholtz-muenchen.de.; Chair of Experimental Genetics, Center of Life and Food Sciences, Weihenstephan, Technische Universität München, Freising, Germany. hrabe@helmholtz-muenchen.de.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2020 Oct 30; Vol. 3 (1), pp. 628. Date of Electronic Publication: 2020 Oct 30.
DOI: 10.1038/s42003-020-01337-x
Abstrakt: The transcription factor PAX6 is involved in the development of the eye and pancreatic islets, besides being associated with sleep-wake cycles. Here, we investigated a point mutation in the RED subdomain of PAX6, previously described in a human patient, to present a comprehensive study of a homozygous Pax6 mutation in the context of adult mammalian metabolism and circadian rhythm. Pax6 Leca2 mice lack appropriate retinal structures for light perception and do not display normal daily rhythmic changes in energy metabolism. Despite β cell dysfunction and decreased insulin secretion, mutant mice have normal glucose tolerance. This is associated with reduced hepatic glucose production possibly due to altered circadian variation in expression of clock and metabolic genes, thereby evading hyperglycemia. Hence, our findings show that while the RED subdomain is important for β cell functional maturity, the Leca2 mutation impacts peripheral metabolism via loss of circadian rhythm, thus revealing pleiotropic effects of PAX6.
Databáze: MEDLINE
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