Partial loss of pancreas endocrine and exocrine cells of human ARX-null mutation: consideration of pancreas differentiation.

Aristaless-related homeobox gene (ARX) mutation leads to several neurological disorders including X-linked lissencephaly with abnormal genitalia (XLAG), West syndrome and Partington syndrome, with XLAG being the most severe form. Although some of the brain pathologies of XLAG have already been described, the crucial extra-brain symptoms are severe growth retardation, transient hyperglycemia and intractable diarrhea. Since ARX expresses in the islets of Langerhans during the embryonic stage, these visceral phenotypes may be related to a loss of ARX function, which develops endocrine cells in the pancreas. We investigated the abnormal pancreatic development of XLAG patients with ARX-null mutation. We performed immunohistochemistry of XLAG pancreases, using the antibodies against glucagon, insulin, somatostatin, pancreatic polypeptide, ghrelin, Brn4, Nkx2.2, Mash1, amylase and pancreatic lipase. As the results, the glucagon- and pancreatic polypeptide-producing cells were found to be completely deficient in the islets of Langerhans. We also discovered marked interstitial fibrosis, small exocrine cells with loss of amylase-producing cells and an enlargement of the central lumen of the glandular acini. These pathological findings indicate that ARX contributes not only to endocrine development, but also to exocrine development of the human pancreas, and its deficiency may lead to the severe phenotypes of XLAG patients.
AuthorsMasayuki Itoh, Yuji Takizawa, Sae Hanai, Shin Okazaki, Rie Miyata, Takeshi Inoue, Takumi Akashi, Masaharu Hayashi, Yu-ichi Goto
JournalDifferentiation; research in biological diversity (Differentiation) 2010 Sep-Oct Vol. 80 Issue 2-3 Pg. 118-22 ISSN: 1432-0436 [Electronic] England
PMID20538404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.
Chemical References
  • ARX protein, human
  • Homeodomain Proteins
  • Transcription Factors
  • Cell Differentiation
  • Classical Lissencephalies and Subcortical Band Heterotopias (genetics)
  • Genitalia, Male (abnormalities)
  • Homeodomain Proteins (genetics)
  • Humans
  • Immunohistochemistry
  • Infant
  • Islets of Langerhans (cytology, embryology)
  • Male
  • Mutation
  • Transcription Factors (genetics)

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