PMID- 19620250
OWN - NLM
STAT- MEDLINE
DCOM- 20100216
LR  - 20211028
IS  - 1479-6821 (Electronic)
IS  - 1351-0088 (Print)
IS  - 1351-0088 (Linking)
VI  - 16
IP  - 4
DP  - 2009 Dec
TI  - Multiple endocrine neoplasia type 1 knockout mice develop parathyroid, 
      pancreatic, pituitary and adrenal tumours with hypercalcaemia, hypophosphataemia 
      and hypercorticosteronaemia.
PG  - 1313-27
LID - 10.1677/ERC-09-0082 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder 
      characterized in man by parathyroid, pancreatic, pituitary and adrenal tumours. 
      The MEN1 gene encodes a 610-amino acid protein (menin) which is a tumour 
      suppressor. To investigate the in vivo role of menin, we developed a mouse model, 
      by deleting Men1 exons 1 and 2 and investigated this for MEN1-associated tumours 
      and serum abnormalities. Men1(+/-) mice were viable and fertile, and 220 
      Men1(+/-) and 94 Men1(+/+) mice were studied between the ages of 3 and 21 months. 
      Survival in Men1(+/-) mice was significantly lower than in Men1(+/+) mice (<68% 
      vs >85%, P<0.01). Men1(+/-) mice developed, by 9 months of age, parathyroid 
      hyperplasia, pancreatic tumours which were mostly insulinomas, by 12 months of 
      age, pituitary tumours which were mostly prolactinomas, and by 15 months 
      parathyroid adenomas and adrenal cortical tumours. Loss of heterozygosity and 
      menin expression was demonstrated in the tumours, consistent with a tumour 
      suppressor role for the Men1 gene. Men1(+/-) mice with parathyroid neoplasms were 
      hypercalcaemic and hypophosphataemic, with inappropriately normal serum 
      parathyroid hormone concentrations. Pancreatic and pituitary tumours expressed 
      chromogranin A (CgA), somatostatin receptor type 2 and vascular endothelial 
      growth factor-A. Serum CgA concentrations in Men1(+/-) mice were not elevated. 
      Adrenocortical tumours, which immunostained for 3-beta-hydroxysteroid 
      dehydrogenase, developed in seven Men1(+/-) mice, but resulted in 
      hypercorticosteronaemia in one out of the four mice that were investigated. Thus, 
      these Men1(+/-) mice are representative of MEN1 in man, and will help in 
      investigating molecular mechanisms and treatments for endocrine tumours.
FAU - Harding, Brian
AU  - Harding B
AD  - Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre 
      for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, 
      University of Oxford, Oxford, UK.
FAU - Lemos, Manuel C
AU  - Lemos MC
FAU - Reed, Anita A C
AU  - Reed AA
FAU - Walls, Gerard V
AU  - Walls GV
FAU - Jeyabalan, Jeshmi
AU  - Jeyabalan J
FAU - Bowl, Michael R
AU  - Bowl MR
FAU - Tateossian, Hilda
AU  - Tateossian H
FAU - Sullivan, Nicky
AU  - Sullivan N
FAU - Hough, Tertius
AU  - Hough T
FAU - Fraser, William D
AU  - Fraser WD
FAU - Ansorge, Olaf
AU  - Ansorge O
FAU - Cheeseman, Michael T
AU  - Cheeseman MT
FAU - Thakker, Rajesh V
AU  - Thakker RV
LA  - eng
GR  - G9825289/MRC_/Medical Research Council/United Kingdom
GR  - MC_UP_1502/1/MRC_/Medical Research Council/United Kingdom
GR  - 913/MSS_/Multiple Sclerosis Society/United Kingdom
GR  - G0501780/MRC_/Medical Research Council/United Kingdom
GR  - 913/DH_/Department of Health/United Kingdom
GR  - MC_U142670371/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090720
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Adrenal Gland Neoplasms/*etiology/pathology
MH  - Animals
MH  - Blotting, Western
MH  - Corticosterone/*blood
MH  - Female
MH  - Hypercalcemia/*etiology/pathology
MH  - Hypophosphatemia/*etiology/pathology
MH  - Immunoenzyme Techniques
MH  - Loss of Heterozygosity
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Multiple Endocrine Neoplasia Type 1/genetics/pathology
MH  - Pancreatic Neoplasms/*etiology/pathology
MH  - Parathyroid Neoplasms/*etiology/pathology
MH  - Pituitary Neoplasms/*etiology/pathology
MH  - Proto-Oncogene Proteins/*physiology
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC4439740
EDAT- 2009/07/22 09:00
MHDA- 2010/02/17 06:00
PMCR- 2009/12/01
CRDT- 2009/07/22 09:00
PHST- 2009/07/22 09:00 [entrez]
PHST- 2009/07/22 09:00 [pubmed]
PHST- 2010/02/17 06:00 [medline]
PHST- 2009/12/01 00:00 [pmc-release]
AID - ERC-09-0082 [pii]
AID - ERC090082 [pii]
AID - 10.1677/ERC-09-0082 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2009 Dec;16(4):1313-27. doi: 10.1677/ERC-09-0082. Epub 2009 
      Jul 20.