A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors

Judy S. Crabtree, Peter C. Scacheri, Jerrold M. Ward, Lisa Garrett-Beal, Michael R. Emmert-Buck, Keith A. Edgemon, Dominique Lorang, Steven K. Libutti, Settara C. Chandrasekharappa, Stephen J. Marx, Allen M. Spiegel, Francis S. Collins

Research output: Contribution to journalArticle

341 Citations (Scopus)

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome, characterized primarily by multiple tumors in the parathyroid glands, endocrine pancreas, and anterior pituitary. Other tumors, including gastrinoma, carcinoid, adrenal cortical tumors, angiofibroma, collagenoma, and lipoma, also occur in some patients. Individuals with MEN1 almost always have loss-of-function mutations in the MEN1 gene on chromosome 11, and endocrine tumors arising in these patients usually show somatic loss of the remaining wild-type allele. To examine the role of MEN1 in tumor formation, a mouse model was generated through homologous recombination of the mouse homolog Men1. Homozygous mice die in utero at embryonic days 11.5-12.5, whereas heterozygous mice develop features remarkably similar to those of the human disorder. As early as 9 months, pancreatic islets show a range of lesions from hyperplasia to insulin-producing islet cell tumors, and parathyroid adenomas are also frequently observed. Larger, more numerous tumors involving pancreatic islets, parathyroids, thyroid, adrenal cortex, and pituitary are seen by 16 months. All of the tumors tested to date show loss of the wild-type Men1 allele, further supporting its role as a tumor suppressor gene.

Original languageEnglish (US)
Pages (from-to)1118-1123
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number3
DOIs
StatePublished - Jan 30 2001
Externally publishedYes

Fingerprint

Multiple Endocrine Neoplasia Type 1
Neoplasms
Islets of Langerhans
Islet Cell Adenoma
Alleles
Gastrinoma
Angiofibroma
Parathyroid Neoplasms
Chromosomes, Human, Pair 11
Parathyroid Glands
Lipoma
Homologous Recombination
Adrenal Cortex
Carcinoid Tumor
Tumor Suppressor Genes
Hyperplasia
Thyroid Gland
Insulin
Mutation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Crabtree, J. S., Scacheri, P. C., Ward, J. M., Garrett-Beal, L., Emmert-Buck, M. R., Edgemon, K. A., ... Collins, F. S. (2001). A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. Proceedings of the National Academy of Sciences of the United States of America, 98(3), 1118-1123. https://doi.org/10.1073/pnas.98.3.1118

A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. / Crabtree, Judy S.; Scacheri, Peter C.; Ward, Jerrold M.; Garrett-Beal, Lisa; Emmert-Buck, Michael R.; Edgemon, Keith A.; Lorang, Dominique; Libutti, Steven K.; Chandrasekharappa, Settara C.; Marx, Stephen J.; Spiegel, Allen M.; Collins, Francis S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 3, 30.01.2001, p. 1118-1123.

Research output: Contribution to journalArticle

Crabtree, JS, Scacheri, PC, Ward, JM, Garrett-Beal, L, Emmert-Buck, MR, Edgemon, KA, Lorang, D, Libutti, SK, Chandrasekharappa, SC, Marx, SJ, Spiegel, AM & Collins, FS 2001, 'A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors', Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 3, pp. 1118-1123. https://doi.org/10.1073/pnas.98.3.1118
Crabtree, Judy S. ; Scacheri, Peter C. ; Ward, Jerrold M. ; Garrett-Beal, Lisa ; Emmert-Buck, Michael R. ; Edgemon, Keith A. ; Lorang, Dominique ; Libutti, Steven K. ; Chandrasekharappa, Settara C. ; Marx, Stephen J. ; Spiegel, Allen M. ; Collins, Francis S. / A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 3. pp. 1118-1123.
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