PMID- 12782272
OWN - NLM
STAT- MEDLINE
DCOM- 20040309
LR  - 20190910
IS  - 0925-4773 (Print)
IS  - 0925-4773 (Linking)
VI  - 120
IP  - 5
DP  - 2003 May
TI  - Genetic ablation of the tumor suppressor menin causes lethality at mid-gestation 
      with defects in multiple organs.
PG  - 549-60
AB  - Patients suffering from multiple endocrine neoplasia type 1 (MEN1) are 
      predisposed to multiple endocrine tumors. The MEN1 gene product, menin, is 
      expressed in many embryonic, as well as adult tissues, and interacts with several 
      proteins in vitro and in vivo. However, the biological function of menin remains 
      largely unknown. Here we show that disruption of the Men1 gene in mice causes 
      embryonic lethality at E11.5-E13.5. The Men1 null mutant embryos appeared smaller 
      in size, frequently with body haemorrhages and oedemas, and a substantial 
      proportion of them showed disclosure of the neural tube. Histological analysis 
      revealed an abnormal development of the nervous system and heart hypotrophy in 
      some Men1 null embryos. Furthermore, Men1 null livers generally displayed an 
      altered organization of the epithelial and hematopoietic compartments associated 
      with enhanced apoptosis. Chimerism analysis of embryos generated by injection of 
      Men1 null ES cells, showed that cells lacking menin do not seem to have a general 
      cell-autonomous defect. However, primary Men1 null embryonic fibroblasts entered 
      senescence earlier than their wild-type counterparts. Despite normal 
      proliferation ability, Men1 null ES cells exhibited a deficiency to form embryoid 
      bodies, suggesting an impaired differentiation capacity in these cells. The 
      present study demonstrates that menin plays an important role in the embryonic 
      development of multiple organs in addition to its proposed role in tumor 
      suppression.
FAU - Bertolino, Philippe
AU  - Bertolino P
AD  - International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, 
      F-69008 Lyon, France.
FAU - Radovanovic, Ivan
AU  - Radovanovic I
FAU - Casse, Huguette
AU  - Casse H
FAU - Aguzzi, Adriano
AU  - Aguzzi A
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
PL  - Ireland
TA  - Mech Dev
JT  - Mechanisms of development
JID - 9101218
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Apoptosis
MH  - Blotting, Western
MH  - Cell Differentiation
MH  - Cell Division
MH  - Cellular Senescence
MH  - Fibroblasts/metabolism
MH  - Genetic Vectors
MH  - Genotype
MH  - Heart/embryology
MH  - Hypertrophy/pathology
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Liver/cytology/embryology/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Models, Genetic
MH  - Mutation
MH  - Myocardium/metabolism
MH  - Neural Crest/embryology
MH  - Proto-Oncogene Proteins/*genetics/metabolism/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
EDAT- 2003/06/05 05:00
MHDA- 2004/03/10 05:00
CRDT- 2003/06/05 05:00
PHST- 2003/06/05 05:00 [pubmed]
PHST- 2004/03/10 05:00 [medline]
PHST- 2003/06/05 05:00 [entrez]
AID - S092547730300039X [pii]
AID - 10.1016/s0925-4773(03)00039-x [doi]
PST - ppublish
SO  - Mech Dev. 2003 May;120(5):549-60. doi: 10.1016/s0925-4773(03)00039-x.