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Role of large MAF transcription factors in the mouse endocrine pancreas

Ahmed M Abdellatif1, Kiyohito Ogata, Takashi Kudo

  • 1Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

Experimental Animals
|April 28, 2015
PubMed

Insights

Large MAF transcription factors, Mafa and Mafb, are crucial for maintaining insulin levels in embryonic development and regulating fasting blood glucose in adult mice with Mafa deficiency.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • The MAF family of transcription factors includes small and large MAFs, with large MAFs being homologs of v-Maf.
  • Large MAF transcription factors play roles in various biological processes, including development and cell differentiation.

Purpose of the Study:

  • To investigate the role of large MAF transcription factors, specifically Mafa and Mafb, in the development and function of the endocrine pancreas.
  • To elucidate the contribution of Mafa and Mafb to insulin production and blood glucose regulation.

Main Methods:

  • Analysis of Mafa gene knockout mice (Mafa(-/-)) and compound Mafa(-/-);Mafb(-/-) and Mafa(-/-);Mafb(+/-) knockout mice.
  • Quantification of Ins1 and Ins2 transcripts and insulin protein levels at embryonic day 18.5.
  • Assessment of islet structure and insulin-positive cell numbers in knockout mice.
  • Measurement of fasting blood glucose levels in adult Mafa(-/-);Mafb(+/-) mice.

Main Results:

  • Mafa(-/-) mice exhibited reduced insulin transcripts and protein levels at embryonic day 18.5.
  • Mafa(-/-);Mafb(-/-) mice showed a drastic reduction (less than 10%) in insulin transcript and protein compared to wild-type mice, indicating a cooperative role of Mafa and Mafb in embryonic insulin maintenance.
  • Mafb appears to play a dominant role in embryonic beta-cell development, as the number of insulin-positive cells was not decreased in Mafa(-/-) or Mafa(-/-);Mafb(+/-) mice.
  • Adult Mafa(-/-);Mafb(+/-) mice displayed higher fasting blood glucose levels than single Mafa(-/-) mice, highlighting Mafb's importance in regulating blood glucose in a Mafa-deficient background.

Conclusions:

  • Mafa is essential for maintaining normal insulin levels during embryonic development.
  • Mafb is critical for regulating fasting blood glucose levels in adult mice lacking functional Mafa.
  • Mafa and Mafb exhibit distinct but cooperative roles in pancreatic islet development and glucose homeostasis.

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