PMID- 32348957
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240306
IS  - 2049-3614 (Print)
IS  - 2049-3614 (Electronic)
IS  - 2049-3614 (Linking)
VI  - 9
IP  - 5
DP  - 2020 May
TI  - Genetic background influences tumour development in heterozygous Men1 knockout 
      mice.
PG  - 426-437
LID - 10.1530/EC-20-0103 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder caused 
      by MEN1 germline mutations, is characterised by parathyroid, pancreatic and 
      pituitary tumours. MEN1 mutations also cause familial isolated primary 
      hyperparathyroidism (FIHP), a milder condition causing hyperparathyroidism only. 
      Identical mutations can cause either MEN1 or FIHP in different families, thereby 
      implicating a role for genetic modifiers in altering phenotypic expression of 
      tumours. We therefore investigated the effects of genetic background and 
      potential for genetic modifiers on tumour development in adult Men1+/- mice, 
      which develop tumours of the parathyroids, pancreatic islets, anterior pituitary, 
      adrenal cortex and gonads, that had been backcrossed to generate C57BL/6 and 
      129S6/SvEv congenic strains. A total of 275 Men1+/- mice, aged 5-26 months were 
      macroscopically studied, and this revealed that genetic background significantly 
      influenced the development of pituitary, adrenal and ovarian tumours, which 
      occurred in mice over 12 months of age and more frequently in C57BL/6 females, 
      129S6/SvEv males and 129S6/SvEv females, respectively. Moreover, pituitary and 
      adrenal tumours developed earlier, in C57BL/6 males and 129S6/SvEv females, 
      respectively, and pancreatic and testicular tumours developed earlier in 
      129S6/SvEv males. Furthermore, glucagon-positive staining pancreatic tumours 
      occurred more frequently in 129S6/SvEv Men1+/- mice. Whole genome sequence 
      analysis of 129S6/SvEv and C57BL/6 Men1+/- mice revealed >54,000 different 
      variants in >300 genes. These included, Coq7, Dmpk, Ccne2, Kras, Wnt2b, Il3ra and 
      Tnfrsf10a, and qRT-PCR analysis revealed that Kras was significantly higher in 
      pituitaries of male 129S6/SvEv mice. Thus, our results demonstrate that Kras and 
      other genes could represent possible genetic modifiers of Men1.
FAU - Lines, Kate E
AU  - Lines KE
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Headington, Oxford, UK.
FAU - Javid, Mahsa
AU  - Javid M
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Headington, Oxford, UK.
FAU - Reed, Anita A C
AU  - Reed AAC
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Headington, Oxford, UK.
FAU - Walls, Gerard V
AU  - Walls GV
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Headington, Oxford, UK.
FAU - Stevenson, Mark
AU  - Stevenson M
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Headington, Oxford, UK.
FAU - Simon, Michelle
AU  - Simon M
AD  - MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, UK.
FAU - Kooblall, Kreepa G
AU  - Kooblall KG
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Headington, Oxford, UK.
FAU - Piret, Sian E
AU  - Piret SE
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Headington, Oxford, UK.
FAU - Christie, Paul T
AU  - Christie PT
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Headington, Oxford, UK.
FAU - Newey, Paul J
AU  - Newey PJ
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Headington, Oxford, UK.
FAU - Mallon, Ann-Marie
AU  - Mallon AM
AD  - MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, UK.
FAU - Thakker, Rajesh V
AU  - Thakker RV
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Headington, Oxford, UK.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - G9825289/MRC_/Medical Research Council/United Kingdom
GR  - MC_U142684171/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PL  - England
TA  - Endocr Connect
JT  - Endocrine connections
JID - 101598413
PMC - PMC7274560
OTO - NOTNLM
OT  - genetic modifiers
OT  - menin
OT  - mouse strain
OT  - pancreatic neuroendocrine tumour
OT  - pituitary
EDAT- 2020/04/30 06:00
MHDA- 2020/04/30 06:01
PMCR- 2020/04/28
CRDT- 2020/04/30 06:00
PHST- 2020/04/17 00:00 [received]
PHST- 2020/04/28 00:00 [accepted]
PHST- 2020/04/30 06:00 [pubmed]
PHST- 2020/04/30 06:01 [medline]
PHST- 2020/04/30 06:00 [entrez]
PHST- 2020/04/28 00:00 [pmc-release]
AID - EC-20-0103.R1 [pii]
AID - EC-20-0103 [pii]
AID - 10.1530/EC-20-0103 [doi]
PST - ppublish
SO  - Endocr Connect. 2020 May;9(5):426-437. doi: 10.1530/EC-20-0103.