Proapoptosis and antiapoptosis-related molecules during postnatal pancreas development in control and nonobese diabetic mice: relationship with innervation

Lab Invest. 2003 Feb;83(2):227-39. doi: 10.1097/01.lab.0000053914.93282.a5.


The mouse pancreas, an immature organ at birth, reaches its adult size and morphology after weaning (3 weeks of age). Around this time, apoptotic phenomena and various types of macrophages are normally present. During development, Fas-Fas ligand (FasL) interactions are known to play a role in apoptotic events involved in tissue remodeling and elimination of damaged cells, and macrophages are routinely observed near apoptotic cells. Apoptosis and Fas-FasL interactions are also thought to be involved in the pathogenesis of autoimmune diseases, particularly type 1 diabetes (T1D). Therefore, we used early postnatal mouse pancreata from three control strains (C57BL/6, DBA/2, BALB/c) and from two strains with the nonobese diabetic (NOD)-related genetic background (the spontaneous T1D NOD model and the lymphocyte-deficient NODscid strain) to study apoptotic phenomena together with the molecular and immunohistochemical expression of proapoptosis (Fas, FasL) and antiapoptosis (Bcl-2) proteins. First, although no major difference in the numbers of total pancreatic apoptotic cells was noted among strains, significantly more FasL(+) expression was detected immunohistochemically in mice with the NOD genetic background than in control pancreata from birth to 1 month of age. Second, FasL(+), Fas(+), and Bcl-2(+) structures seemed to be associated with innervation, regardless of the strain and age. Third, in control and NOD strains, nerves (identified by immunohistochemical labeling of peripherin or neurofilament 200), were often observed in periductular and peri-insular areas. Finally, some peripherin-positive nerves expressed the interferon-inducible protein-10 chemokine, and various types of macrophages were found to be in close proximity. These data highlight an overlooked, innervation-related aspect of normal mouse postnatal pancreas development with possible implications in T1D pathogenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis*
  • DNA Primers / chemistry
  • Diabetes Mellitus, Type 2 / metabolism*
  • Fas Ligand Protein
  • Female
  • Image Processing, Computer-Assisted
  • Immunoenzyme Techniques
  • In Situ Nick-End Labeling
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Pancreas / growth & development
  • Pancreas / innervation*
  • Pancreas / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Species Specificity
  • fas Receptor / metabolism*


  • DNA Primers
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • fas Receptor