PMID- 12819299
OWN - NLM
STAT- MEDLINE
DCOM- 20040511
LR  - 20061115
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 17
IP  - 9
DP  - 2003 Sep
TI  - Heterozygous Men1 mutant mice develop a range of endocrine tumors mimicking 
      multiple endocrine neoplasia type 1.
PG  - 1880-92
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome characterized 
      by the occurrence of multiple endocrine tumors of the parathyroid, pancreas, and 
      anterior pituitary in patients. To study tumorigenesis related to the MEN1 
      syndrome, we have generated Men1 knockout mice using the gene targeting approach. 
      Heterozygous Men1 mutant mice developed the same range of major endocrine tumors 
      as is seen in MEN1 patients, affecting the parathyroid, pancreatic islets, 
      pituitary and adrenal glands, as well as the thyroid, and exhibiting multistage 
      tumor progression with metastatic potential. In particular, extrapancreatic 
      gastrinoma, pancreatic glucagonoma, and mixed hormone-producing tumors in islets 
      were observed. In addition, there was a high incidence of gonadal tumors of 
      endocrine origin, i.e. Leydig cell tumors, and ovary sex-cord stromal cell tumors 
      in heterozygous Men1 mutant mice. Hormonal disturbance, such as abnormal PTH and 
      insulin levels, was also observed in these mice. These tumors were associated 
      with loss of heterozygosity of the wild-type Men1 allele, suggesting that menin 
      is involved in suppressing the development of these endocrine tumors. All of 
      these features are reminiscent of MEN1 symptoms in humans and establish 
      heterozygous Men1 mutant mice as a suitable model for this disease.
FAU - Bertolino, Philippe
AU  - Bertolino P
AD  - Laboratory of Genetics, Centre National de la Recherche Scientifique, Faculty of 
      Medicine, University of Lyon, Lyon, France.
FAU - Tong, Wei-Min
AU  - Tong WM
FAU - Galendo, Dominique
AU  - Galendo D
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 - 20030620
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Animals
MH  - *Disease Models, Animal
MH  - Endocrine System/pathology
MH  - Genes, Dominant
MH  - Heterozygote
MH  - Mice
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/metabolism
MH  - Mutation
MH  - Proto-Oncogene Proteins/*genetics/metabolism
EDAT- 2003/06/24 05:00
MHDA- 2004/05/12 05:00
CRDT- 2003/06/24 05:00
PHST- 2003/06/24 05:00 [pubmed]
PHST- 2004/05/12 05:00 [medline]
PHST- 2003/06/24 05:00 [entrez]
AID - me.2003-0154 [pii]
AID - 10.1210/me.2003-0154 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2003 Sep;17(9):1880-92. doi: 10.1210/me.2003-0154. Epub 2003 Jun 
      20.