PMID- 19587266
OWN - NLM
STAT- MEDLINE
DCOM- 20091005
LR  - 20211028
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Linking)
VI  - 203
IP  - 1
DP  - 2009 Oct
TI  - Genetic background influences embryonic lethality and the occurrence of neural 
      tube defects in Men1 null mice: relevance to genetic modifiers.
PG  - 133-42
LID - 10.1677/JOE-09-0124 [doi]
AB  - Germline mutations of the multiple endocrine neoplasia type 1 (MEN1) gene cause 
      parathyroid, pancreatic and pituitary tumours in man. MEN1 mutations also cause 
      familial isolated primary hyperparathyroidism (FIHP) and the same MEN1 mutations, 
      in different families, can cause either FIHP or MEN1. This suggests a role for 
      genetic background and modifier genes in altering the expression of a mutation. 
      We investigated the effects of genetic background on the phenotype of embryonic 
      lethality that occurs in a mouse model for MEN1. Men1(+/-) mice were backcrossed 
      to generate C57BL/6 and 129S6/SvEv incipient congenic strains, and used to obtain 
      homozygous Men1(-/-) mice. No viable Men1(-/-) mice were obtained. The analysis 
      of 411 live embryos obtained at 9.5-16.5 days post-coitum (dpc) revealed that 
      significant deviations from the expected Mendelian 1:2:1 genotype ratio were 
      first observed at 12.5 and 14.5 dpc in the 129S6/SvEv and C57BL/6 strains 
      respectively (P<0.05). Moreover, live Men1(-/-) embryos were absent by 13.5 and 
      15.5 dpc in the 129S6/SvEv and C57BL/6 strains respectively thereby indicating an 
      earlier lethality by 2 days in the 129S6/SvEv strain (P<0.01). Men1(-/-) embryos 
      had macroscopic haemorrhages, and histology and optical projection tomography 
      revealed them to have internal haemorrhages, myocardial hypotrophy, pericardial 
      effusion, hepatic abnormalities and neural tube defects. The neural tube defects 
      occurred exclusively in 129S6/SvEv embryos (21 vs 0%, P<0.01). Thus, our findings 
      demonstrate the importance of genetic background in influencing the phenotypes of 
      embryonic lethality and neural tube defects in Men1(-/-) mice, and implicate a 
      role for genetic modifiers.
FAU - Lemos, Manuel C
AU  - Lemos MC
AD  - Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre 
      for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of 
      Oxford, Headington, Oxford OX3 7LJ, UK.
FAU - Harding, Brian
AU  - Harding B
FAU - Reed, Anita A C
AU  - Reed AA
FAU - Jeyabalan, Jeshmi
AU  - Jeyabalan J
FAU - Walls, Gerard V
AU  - Walls GV
FAU - Bowl, Michael R
AU  - Bowl MR
FAU - Sharpe, James
AU  - Sharpe J
FAU - Wedden, Sarah
AU  - Wedden S
FAU - Moss, Julie E
AU  - Moss JE
FAU - Ross, Allyson
AU  - Ross A
FAU - Davidson, Duncan
AU  - Davidson D
FAU - Thakker, Rajesh V
AU  - Thakker RV
LA  - eng
GR  - G9825289/MRC_/Medical Research Council/United Kingdom
GR  - MC_U127574434/MRC_/Medical Research Council/United Kingdom
GR  - G9825289, 2004/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_U127527203/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090708
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Animals
MH  - Embryo, Mammalian/*pathology
MH  - Female
MH  - *Genes, Lethal
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neural Tube Defects/*genetics/pathology
MH  - *Phenotype
MH  - Pregnancy
MH  - Proto-Oncogene Proteins/*genetics
EDAT- 2009/07/10 09:00
MHDA- 2009/10/06 06:00
CRDT- 2009/07/10 09:00
PHST- 2009/07/10 09:00 [entrez]
PHST- 2009/07/10 09:00 [pubmed]
PHST- 2009/10/06 06:00 [medline]
AID - JOE-09-0124 [pii]
AID - 10.1677/JOE-09-0124 [doi]
PST - ppublish
SO  - J Endocrinol. 2009 Oct;203(1):133-42. doi: 10.1677/JOE-09-0124. Epub 2009 Jul 8.