PMID- 18772165
OWN - NLM
STAT- MEDLINE
DCOM- 20090710
LR  - 20220310
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Linking)
VI  - 199
IP  - 2
DP  - 2008 Nov
TI  - Tumour suppressor menin is essential for development of the pancreatic endocrine 
      cells.
PG  - 287-98
LID - 10.1677/JOE-08-0289 [doi]
AB  - Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene predispose 
      patients to MEN1 that affects mainly endocrine tissues, suggesting important 
      physiological functions of the gene in adult endocrine cells. Homozygous 
      disruption of Men1 in mice causes embryonic lethality, whereas the eventual 
      involvement of the gene in embryonic development of the endocrine cells remains 
      unknown. Here, we show that homozygous Men1 knockout mice demonstrate a reduced 
      number of glucagon-positive cells in the E12.5 pancreatic bud associated with 
      apoptosis, whereas the exocrine pancreas development in these mice is not 
      affected. Our data suggest that menin is involved in the survival of the early 
      pancreatic endocrine cells during the first developmental transition. 
      Furthermore, chimerism assay revealed that menin has an autonomous and specific 
      effect on the development of islet cells. In addition, using pancreatic bud 
      culture mimicking the differentiation of alpha- and beta-cells during the second 
      transition, we show that loss of menin leads to the failure of endocrine cell 
      development, altered pancreatic structure and a markedly decreased number of 
      cells expressing neurogenin 3, indicating that menin is also required at this 
      stage of the endocrine pancreas development. Taken together, our results suggest 
      that menin plays an indispensable role in the development of the pancreatic 
      endocrine cells.
FAU - Fontaniere, Sandra
AU  - Fontaniere S
AD  - CNRS UMR2501, Laboratoire Genetique Moleculaire, Signalisation et Cancer, 
      Universite Claude Bernard Lyon, Lyon F-69008, France.
FAU - Duvillie, Bertrand
AU  - Duvillie B
FAU - Scharfmann, Raphael
AU  - Scharfmann R
FAU - Carreira, Christine
AU  - Carreira C
FAU - Wang, Zhao-Qi
AU  - Wang ZQ
FAU - Zhang, Chang-Xian
AU  - Zhang CX
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080904
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurog3 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Basic Helix-Loop-Helix Transcription Factors/metabolism
MH  - Endocrine Cells/*cytology/*metabolism
MH  - Epithelial Cells/cytology/metabolism/physiology
MH  - Fluorescent Antibody Technique
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - In Situ Nick-End Labeling
MH  - In Vitro Techniques
MH  - Mice
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/metabolism
MH  - Pancreas/cytology/embryology/*metabolism
MH  - Proto-Oncogene Proteins/genetics/metabolism/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2008/09/06 09:00
MHDA- 2009/07/11 09:00
CRDT- 2008/09/06 09:00
PHST- 2008/09/06 09:00 [pubmed]
PHST- 2009/07/11 09:00 [medline]
PHST- 2008/09/06 09:00 [entrez]
AID - JOE-08-0289 [pii]
AID - 10.1677/JOE-08-0289 [doi]
PST - ppublish
SO  - J Endocrinol. 2008 Nov;199(2):287-98. doi: 10.1677/JOE-08-0289. Epub 2008 Sep 4.