Pancreatic α-cell specific deletion of mouse Arx leads to α-cell identity loss

PLoS One. 2013 Jun 13;8(6):e66214. doi: 10.1371/journal.pone.0066214. Print 2013.


The specification and differentiation of pancreatic endocrine cell populations (α-, β-, δ, PP- and ε-cells) is orchestrated by a combination of transcriptional regulators. In the pancreas, Aristaless-related homeobox gene (Arx) is expressed first in the endocrine progenitors and then restricted to glucagon-producing α-cells. While the functional requirement of Arx in early α-cell specification has been investigated, its role in maintaining α-cell identity has yet to be explored. To study this later role of Arx, we have generated mice in which the Arx gene has been ablated specifically in glucagon-producing α-cells. Lineage-tracing studies and immunostaining analysis for endocrine hormones demonstrate that ablation of Arx in neonatal α-cells results in an α-to-β-like conversion through an intermediate bihormonal state. Furthermore, these Arx-deficient converted cells express β-cell markers including Pdx1, MafA, and Glut2. Surprisingly, short-term ablation of Arx in adult mice does not result in a similar α-to-β-like conversion. Taken together, these findings reveal a potential temporal requirement for Arx in maintaining α-cell identity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Cell Lineage / genetics
  • Female
  • Gene Deletion*
  • Gene Expression
  • Glucagon / genetics
  • Glucagon / metabolism
  • Glucagon-Secreting Cells / metabolism*
  • Homeodomain Proteins / genetics*
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin-Secreting Cells / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Transcription Factors / genetics*


  • ARX protein, mouse
  • Biomarkers
  • Homeodomain Proteins
  • Insulin
  • Transcription Factors
  • Glucagon