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Chhabra, N.F. ; Amarie, O.V. ; Wu, M. ; Amend, A.-L. ; Rubey, M. ; Gradinger, D. ; Irmler, M. ; Beckers, J. ; Rathkolb, B. ; Wolf, E.* ; Feuchtinger, A. ; Huypens, P. ; Teperino, R. ; Rozman, J. ; Przemeck, G.K.H. ; Hrabě de Angelis, M.

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

Comm. Biol. 3:628 (2020)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 beta 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 beta cell functional maturity, the Leca2 mutation impacts peripheral metabolism via loss of circadian rhythm, thus revealing pleiotropic effects of PAX6. Nirav Chhabra et al. characterize adult mice carrying a homozygous mutation in Pax6 that was identified in a patient with foveal hypoplasia. They find that the Pax6 point mutation has pleiotropic effects, including defects in the mouse retinal structures, loss of the optic nerve, changes in energy metabolism and circadian rhythms, and dysregulation of genes expressed in the pancreas.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Paired Domain; Early-onset; Mouse; Gene; Aniridia; Reveals; Transcription; Expression; Identification; Neurogenesis
ISSN (print) / ISBN 2399-3642
e-ISSN 2399-3642
Journal Communications Biology
Quellenangaben Volume: 3, Issue: 1, Pages: , Article Number: 628 Supplement: ,
Publisher Springer
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Research Unit Analytical Pathology (AAP)
Grants Helmholtz Alliance 'Aging and Metabolic Programming, AMPro'
German Center for Diabetes Research (DZD)