PMID- 28420716
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240214
IS  - 2049-3614 (Print)
IS  - 2049-3614 (Electronic)
IS  - 2049-3614 (Linking)
VI  - 6
IP  - 4
DP  - 2017 May
TI  - A MEN1 pancreatic neuroendocrine tumour mouse model under temporal control.
PG  - 232-242
LID - 10.1530/EC-17-0040 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder 
      characterised by occurrence of parathyroid tumours and neuroendocrine tumours 
      (NETs) of the pancreatic islets and anterior pituitary. The MEN1 gene, encoding 
      menin, is a tumour suppressor, but its precise role in initiating in vivo 
      tumourigenesis remains to be elucidated. The availability of a temporally 
      controlled conditional MEN1 mouse model would greatly facilitate the study of 
      such early tumourigenic events, and overcome the limitations of other MEN1 
      knockout models, in which menin is lost from conception or tumour development 
      occurs asynchronously. To generate a temporally controlled conditional mouse 
      model, we crossbred mice with the MEN1 gene floxed by LoxP sites (Men1(L/L) ), 
      and mice expressing tamoxifen-inducible Cre recombinase under the control of the 
      rat insulin promoter (RIP2-CreER), to establish a pancreatic beta-cell-specific NET 
      model under temporal control (Men1(L/L) /RIP2-CreER). Men1(L/L) /RIP2-CreER mice 
      aged ~3 months were given tamoxifen in the diet for 5 days, and pancreata 
      harvested 2-2.5, 2.9-3.5 and 4.5-5.5 months later. Control mice did not express 
      Cre and did not receive tamoxifen. Immunostaining of pancreata from 
      tamoxifen-treated Men1(L/L) /RIP2-CreER mice, compared to control mice, showed at 
      all ages: loss of menin in all islets; increased islet area (>4.2-fold); 
      increased proliferation of insulin immunostaining beta-cells (>2.3-fold) and 
      decreased proliferation of glucagon immunostaining alpha-cells (>1.7-fold). There 
      were no gender and apoptotic or proliferation differences, and extra-pancreatic 
      tumours were not detected. Thus, we have established a mouse model (Men1(L/L) 
      /RIP2-CreER) to study early events in the development of pancreatic beta-cell NETs.
CI  - (c) 2017 The authors.
FAU - Lines, K E
AU  - Lines KE
FAU - Vas Nunes, R P
AU  - Vas Nunes RP
FAU - Frost, M
AU  - Frost M
AD  - Academic Endocrine UnitOCDEM, University of Oxford, Churchill Hospital, Oxford, 
      UK.
FAU - Yates, C J
AU  - Yates CJ
AD  - Academic Endocrine UnitOCDEM, University of Oxford, Churchill Hospital, Oxford, 
      UK.
FAU - Stevenson, M
AU  - Stevenson M
AD  - Academic Endocrine UnitOCDEM, University of Oxford, Churchill Hospital, Oxford, 
      UK.
FAU - Thakker, R V
AU  - Thakker RV
AD  - Academic Endocrine UnitOCDEM, University of Oxford, Churchill Hospital, Oxford, 
      UK rajesh.thakker@ndm.ox.ac.uk.
LA  - eng
GR  - G1000467/MRC_/Medical Research Council/United Kingdom
GR  - G9825289/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20170418
PL  - England
TA  - Endocr Connect
JT  - Endocrine connections
JID - 101598413
PMC - PMC5632719
OTO - NOTNLM
OT  - mouse model
OT  - multiple endocrine neoplasia
OT  - pancreatic islet
OT  - tamoxifen inducible
EDAT- 2017/04/20 06:00
MHDA- 2017/04/20 06:01
PMCR- 2017/04/18
CRDT- 2017/04/20 06:00
PHST- 2017/04/11 00:00 [received]
PHST- 2017/04/18 00:00 [accepted]
PHST- 2017/04/20 06:00 [pubmed]
PHST- 2017/04/20 06:01 [medline]
PHST- 2017/04/20 06:00 [entrez]
PHST- 2017/04/18 00:00 [pmc-release]
AID - EC-17-0040 [pii]
AID - EC170040 [pii]
AID - 10.1530/EC-17-0040 [doi]
PST - ppublish
SO  - Endocr Connect. 2017 May;6(4):232-242. doi: 10.1530/EC-17-0040. Epub 2017 Apr 18.