Of mice and MEN1: Insulinomas in a conditional mouse knockout

Judy S. Crabtree, Peter C. Scacheri, Jerrold M. Ward, Sara R. McNally, Gary P. Swain, Cristina Montagna, Jeffrey H. Hager, Douglas Hanahan, Helena Edlund, Mark A. Magnuson, Lisa Garrett-Beal, A. Lee Burns, Thomas Ried, Settara C. Chandrasekharappa, Stephen J. Marx, Allen M. Spiegel, Francis S. Collins

Research output: Contribution to journalArticle

159 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6075-6085
Number of pages11
JournalMolecular and cellular biology
Volume23
Issue number17
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Crabtree, J. S., Scacheri, P. C., Ward, J. M., McNally, S. R., Swain, G. P., Montagna, C., Hager, J. H., Hanahan, D., Edlund, H., Magnuson, M. A., Garrett-Beal, L., Burns, A. L., Ried, T., Chandrasekharappa, S. C., Marx, S. J., Spiegel, A. M., & Collins, F. S. (2003). Of mice and MEN1: Insulinomas in a conditional mouse knockout. Molecular and cellular biology, 23(17), 6075-6085. https://doi.org/10.1128/MCB.23.17.6075-6085.2003