RGD Reference Report - Pancreatic beta-cell-specific ablation of the multiple endocrine neoplasia type 1 (MEN1) gene causes full penetrance of insulinoma development in mice. - Rat Genome Database

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Pancreatic beta-cell-specific ablation of the multiple endocrine neoplasia type 1 (MEN1) gene causes full penetrance of insulinoma development in mice.

Authors: Bertolino, P  Tong, WM  Herrera, PL  Casse, H  Zhang, CX  Wang, ZQ 
Citation: Bertolino P, etal., Cancer Res. 2003 Aug 15;63(16):4836-41.
RGD ID: 2317292
Pubmed: PMID:12941803   (View Abstract at PubMed)

The function of the predisposition gene to multiple endocrine neoplasia type 1 (MEN1) syndrome remains largely unknown. Previous studies demonstrated that null mutation of the Men1 gene caused mid-gestation lethality in mice, whereas heterozygous Men1 knockout mice developed multiple endocrine tumors late in life. To seek direct evidence on the causal role of menin in suppressing tumor development, we generated mice in which the Men1 gene was disrupted specifically in pancreatic beta cells. These mice began to develop hyperplastic islets at as early as 2 months of age and insulinomas at 6 months of age. The islet lesions exhibited features of multistage tumor progression, including beta-cell dedifferentiation, angiogenesis, and altered expression of both E-cadherin and beta-catenin. Additionally, disturbance of blood insulin and glucose levels correlated with tumor development, mimicking human MEN1 symptoms. Our data indicate that this strain of mice provides a powerful tool for the study of the mechanisms of tumorigenesis related to MEN1 disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MEN1Humaninsulinoma disease_progressionISORGD:736444DNA:deletion:exonRGD 
Men1Ratinsulinoma disease_progressionISORGD:736444DNA:deletion:exonRGD 
Men1Mouseinsulinoma disease_progressionIMP DNA:deletion:exonRGD 

Objects Annotated

Genes (Rattus norvegicus)
Men1  (menin 1)

Genes (Mus musculus)
Men1  (multiple endocrine neoplasia 1)

Genes (Homo sapiens)
MEN1  (menin 1)


Additional Information