Experimental Animals
Online ISSN : 1881-7122
Print ISSN : 1341-1357
ISSN-L : 0007-5124
Original
Uncovering the role of MAFB in glucagon production and secretion in pancreatic α-cells using a new α-cell-specific Mafb conditional knockout mouse model
Yu-Hsin ChangMegumi C. KatohAhmed M. AbdellatifGuli XiafukaitiAbdelaziz ElzeftawyMasami OjimaSeiya MizunoAkihiro KunoSatoru Takahashi
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JOURNALS OPEN ACCESS

2020 Volume 69 Issue 2 Pages 178-188

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Abstract

Cre/loxP is a site-specific recombination system extensively used to enable the conditional deletion or activation of target genes in a spatial- and/or temporal-specific manner. A number of pancreatic-specific Cre driver mouse lines have been broadly established for studying the development, function and pathology of pancreatic cells. However, only a few models are currently available for glucagon-producing α-cells. Disagreement exists over the role of the MAFB transcription factor in glucagon expression during postnatal life, which might be due to the lack of α-cell-specific Cre driver mice. In the present study, we established a novel Gcg-Cre knock-in mouse line with the Cre transgene expressed under the control of the preproglucagon (Gcg) promoter without disrupting the endogenous Gcg gene expression. Then, we applied this newly developed Gcg-Cre mouse line to generate a new α-cell-specific Mafb conditional knockout mouse model (MafbΔGcg). Not only α-cell number but also glucagon production were significantly decreased in MafbΔGcg mice compared to control littermates, suggesting an indispensable role of MAFB in both α-cell development and function. Taken together, our newly developed Gcg-Cre mouse line, which was successfully utilized to uncover the role of MAFB in α-cells, is a useful tool for genetic manipulation in pancreatic α-cells, providing a new platform for future studies in this field.

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© 2020 Japanese Association for Laboratory Animal Science
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