PMID- 12917331
OWN - NLM
STAT- MEDLINE
DCOM- 20030924
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 23
IP  - 17
DP  - 2003 Sep
TI  - Of mice and MEN1: Insulinomas in a conditional mouse knockout.
PG  - 6075-85
AB  - Patients with multiple endocrine neoplasia type 1 (MEN1) develop multiple 
      endocrine tumors, primarily affecting the parathyroid, pituitary, and endocrine 
      pancreas, due to the inactivation of the MEN1 gene. A conditional mouse model was 
      developed to evaluate the loss of the mouse homolog, Men1, in the pancreatic beta 
      cell. Men1 in these mice contains exons 3 to 8 flanked by loxP sites, such that, 
      when the mice are crossed to transgenic mice expressing cre from the rat insulin 
      promoter (RIP-cre), exons 3 to 8 are deleted in beta cells. By 60 weeks of age, 
      >80% of mice homozygous for the floxed Men1 gene and expressing RIP-cre develop 
      multiple pancreatic islet adenomas. The formation of adenomas results in elevated 
      serum insulin levels and decreased blood glucose levels. The delay in tumor 
      appearance, even with early loss of both copies of Men1, implies that additional 
      somatic events are required for adenoma formation in beta cells. Comparative 
      genomic hybridization of beta cell tumor DNA from these mice reveals duplication 
      of chromosome 11, potentially revealing regions of interest with respect to 
      tumorigenesis.
FAU - Crabtree, Judy S
AU  - Crabtree JS
AD  - National Human Genome Research Institute, National Institutes of Health, 
      Bethesda, Maryland 20892, USA.
FAU - Scacheri, Peter C
AU  - Scacheri PC
FAU - Ward, Jerrold M
AU  - Ward JM
FAU - McNally, Sara R
AU  - McNally SR
FAU - Swain, Gary P
AU  - Swain GP
FAU - Montagna, Cristina
AU  - Montagna C
FAU - Hager, Jeffrey H
AU  - Hager JH
FAU - Hanahan, Douglas
AU  - Hanahan D
FAU - Edlund, Helena
AU  - Edlund H
FAU - Magnuson, Mark A
AU  - Magnuson MA
FAU - Garrett-Beal, Lisa
AU  - Garrett-Beal L
FAU - Burns, A Lee
AU  - Burns AL
FAU - Ried, Thomas
AU  - Ried T
FAU - Chandrasekharappa, Settara C
AU  - Chandrasekharappa SC
FAU - Marx, Stephen J
AU  - Marx SJ
FAU - Spiegel, Allen M
AU  - Spiegel AM
FAU - Collins, Francis S
AU  - Collins FS
LA  - eng
GR  - P30 DK050306/DK/NIDDK NIH HHS/United States
GR  - P30 DK50306/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Viral Proteins)
RN  - EC 2.7.7.- (Cre recombinase)
RN  - EC 2.7.7.- (Integrases)
SB  - IM
MH  - Adenoma/*genetics/metabolism/pathology
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Cell Division/genetics
MH  - Cells, Cultured
MH  - Disease-Free Survival
MH  - Genetic Engineering/methods
MH  - Heterozygote
MH  - Homozygote
MH  - Hyperplasia/genetics
MH  - In Situ Hybridization/methods
MH  - Insulin/genetics/metabolism
MH  - Insulinoma/*genetics/metabolism/pathology
MH  - Integrases/genetics
MH  - Islets of Langerhans/pathology/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Pancreatic Neoplasms/*genetics/metabolism/pathology
MH  - Pituitary Gland/pathology
MH  - Promoter Regions, Genetic
MH  - *Proto-Oncogene Proteins
MH  - Sequence Deletion
MH  - Viral Proteins/genetics
PMC - PMC180910
EDAT- 2003/08/15 05:00
MHDA- 2003/09/25 05:00
PMCR- 2003/09/01
CRDT- 2003/08/15 05:00
PHST- 2003/08/15 05:00 [pubmed]
PHST- 2003/09/25 05:00 [medline]
PHST- 2003/08/15 05:00 [entrez]
PHST- 2003/09/01 00:00 [pmc-release]
AID - 0010 [pii]
AID - 10.1128/MCB.23.17.6075-6085.2003 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2003 Sep;23(17):6075-85. doi: 10.1128/MCB.23.17.6075-6085.2003.