Reference SummaryCrabtree JS, Proc Natl Acad Sci U S A 2001 Jan 30;98(3):1118-23

Title

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

Authors

 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

Journal

 Proc Natl Acad Sci U S A

Volume

 98

Issue

 3

Year

 2001

Pages

 1118-23

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.

Links

 J:67128 – MGI References
11158604 – National Library of Medicine/PubMed

Strain Notes

Strain Note
[not specified] Littermate controls for conditional targeted mutant mice.
The genetic background of these mice likely contained either 129S6/SvEvTac or NIH Black Swiss or both.
[not specified]-Men1tm1.1Ctre/+ The mice carrying the conditional allele from which this allele was generated were likely either mixed 129S6/SvEvTac and NIH Black Swiss or inbred 129S6/SvEvTac. Male chimeric mice were bred to either NIH Black Swiss or 129S6/SvEvTac mice to generate heterozygous mice carrying the conditional allele. These mice were crossed to mice "ubiquitously expressing EIIa-cre" transgene on an unspecified genetic background.
[not specified]-Men1tm1Ctre/+ Although the Men1tm1Ctre allele is a floxed, unrecombined conditional allele it caused a very strong phenotype in mice carrying it.
The genetic background was not specified. It was likely either mixed 129S6/SvEvTac and NIH Black Swiss or inbred 129S6/SvEvTac. Male chimeric mice were bred to either NIH Black Swiss or 129S6/SvEvTac mice.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-Men1tm1Ctre/+ Adrenal gland - Cortex carcinoma Adrenal gland - Cortex

0 - 27
[not specified]-Men1tm1Ctre/+ Adrenal gland - Medulla pheochromocytoma Adrenal gland - Medulla

0 - 17
[not specified]-Men1tm1Ctre/+ Lung adenocarcinoma Lung

8.3 - 33
[not specified]-Men1tm1Ctre/+ Ovary adenoma Ovary

8.3
[not specified]-Men1tm1Ctre/+ Pancreas - Acinar cell cyst Pancreas - Acinar cell

observed
[not specified]-Men1tm1Ctre/+ Pancreas - Acinar cell dysplasia - focal Pancreas - Acinar cell

observed
[not specified]-Men1tm1Ctre/+ Pancreas - Islet of Langerhans adenoma Pancreas - Islet of Langerhans

observed - 40
[not specified] Pancreas - Islet of Langerhans adenoma Pancreas - Islet of Langerhans

0
B6;129 Pancreas - Islet of Langerhans adenoma Pancreas - Islet of Langerhans

4.2
[not specified]-Men1tm1.1Ctre/+ Pancreas - Islet of Langerhans adenoma Pancreas - Islet of Langerhans

83
[not specified]-Men1tm1Ctre/+ Pancreas - Islet of Langerhans dysplasia Pancreas - Islet of Langerhans

observed
[not specified]-Men1tm1Ctre/+ Pancreas - Islet of Langerhans hyperplasia Pancreas - Islet of Langerhans

observed - 40
[not specified]-Men1tm1.1Ctre/+ Pancreas - Islet of Langerhans hyperplasia Pancreas - Islet of Langerhans

83
[not specified]-Men1tm1Ctre/+ Parathyroid gland adenoma Parathyroid gland

18 - 29
[not specified]-Men1tm1Ctre/+ Parathyroid gland carcinoma Parathyroid gland

4.0
[not specified]-Men1tm1Ctre/+ Parathyroid gland dysplasia - focal Parathyroid gland

observed
B6;129 Parathyroid gland tumor Parathyroid gland

2.1
[not specified]-Men1tm1Ctre/+ Pituitary gland - Pars distalis adenoma Pituitary gland - Pars distalis

13 - 42
[not specified]-Men1tm1Ctre/+ Prostate gland carcinoma Prostate gland

6.7
[not specified]-Men1tm1Ctre/+ Stomach - Neuroendocrine cell tumor Stomach - Neuroendocrine cell

3.7
[not specified]-Men1tm1Ctre/+ Stomach gastrinoma Stomach

0
[not specified]-Men1tm1Ctre/+ Thyroid gland - Follicular cell adenoma Thyroid gland - Follicular cell

observed
[not specified]-Men1tm1Ctre/+ Thyroid gland cyst Thyroid gland

observed
[not specified]-Men1tm1Ctre/+ (Unspecified organ) tumor (Unspecified organ)

0