Of mice and MEN1: Insulinomas in a conditional mouse knockout.
Mol Cell Biol
; 23(17): 6075-85, 2003 Sep.
Article
em En
| MEDLINE
| ID: mdl-12917331
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Adenoma
/
Proteínas Proto-Oncogênicas
/
Insulinoma
/
Proteínas de Neoplasias
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos