PMID- 30129265
OWN - NLM
STAT- MEDLINE
DCOM- 20191106
LR  - 20240213
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 42
IP  - 11
DP  - 2018 Nov
TI  - Knockdown of Mns1 Increases Susceptibility to Craniofacial Defects Following 
      Gastrulation-Stage Alcohol Exposure in Mice.
PG  - 2136-2143
LID - 10.1111/acer.13876 [doi]
AB  - BACKGROUND: MNS1 (meiosis-specific nuclear structural protein 1) is necessary for 
      motile cilia function, such as sperm flagella or those found in the embryonic 
      primitive node. While little is known regarding the function or expression 
      pattern of MNS1 in the embryo, co-immunoprecipitation experiments in sperm have 
      determined that MNS1 interacts with ciliary proteins, which are also important 
      during development. Establishment of morphogenic gradients is dependent on normal 
      ciliary motion in the primitive node beginning during gastrulation (gestational 
      day [GD] 7 in the mouse, second-third week of pregnancy in humans), a critical 
      window for face, eye, and brain development and particularly susceptible to 
      perturbations of developmental signals. The current study investigates the role 
      of Mns1 in craniofacial defects associated with gastrulation-stage alcohol 
      exposure. METHODS: On GD7, pregnant Mns1(+/-) dams were administered 2 doses of 
      ethanol (5.8 g/kg total) or vehicle 4 hours apart to target gastrulation. On 
      GD17, fetuses were examined for ocular defects by scoring each eye on a scale 
      from 1 to 7 (1 = normal, 2 to 7 = defects escalating in severity). Craniofacial 
      and brain abnormalities were also assessed. RESULTS: Prenatal alcohol exposure 
      (PAE) significantly increased the rate of defects in wild-type fetuses, as PAE 
      fetuses had an incidence rate of 41.18% compared to a 10% incidence rate in 
      controls. Furthermore, PAE interacted with genotype to significantly increase the 
      defect rate and severity in Mns1(+/-) (64.29%) and Mns1(-/-) mice (92.31%). PAE 
      Mns1(-/-) fetuses with severe eye defects also presented with craniofacial 
      dysmorphologies characteristic of fetal alcohol syndrome and midline tissue loss 
      in the brain, palate, and nasal septum. CONCLUSIONS: These data demonstrate that 
      a partial or complete knockdown of Mns1 interacts with PAE to increase the 
      susceptibility to ocular defects and correlating craniofacial and brain 
      anomalies, likely though interaction of alcohol with motile cilia function. These 
      results further our understanding of genetic risk factors that may underlie 
      susceptibility to teratogenic exposures.
CI  - (c) 2018 by the Research Society on Alcoholism.
FAU - Boschen, Karen E
AU  - Boschen KE
AUID- ORCID: 0000-0001-5838-0016
AD  - Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, 
      North Carolina.
FAU - Gong, Henry
AU  - Gong H
AD  - Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, 
      North Carolina.
FAU - Murdaugh, Laura B
AU  - Murdaugh LB
AD  - Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, 
      North Carolina.
FAU - Parnell, Scott E
AU  - Parnell SE
AD  - Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, 
      North Carolina.
AD  - Department of Cell Biology and Physiology, University of North Carolina, Chapel 
      Hill, North Carolina.
LA  - eng
GR  - F32 AA026479/AA/NIAAA NIH HHS/United States
GR  - P60 AA011605/AA/NIAAA NIH HHS/United States
GR  - R00 AA018697/AA/NIAAA NIH HHS/United States
GR  - U01 AA021651/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180910
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Mns1 protein, mouse)
RN  - 0 (Nuclear Proteins)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Cell Cycle Proteins
MH  - Central Nervous System/abnormalities/pathology
MH  - Central Nervous System Depressants/*toxicity
MH  - Craniofacial Abnormalities/*chemically induced/epidemiology/*genetics
MH  - Ethanol/*toxicity
MH  - Eye Abnormalities/chemically induced/epidemiology/pathology
MH  - Female
MH  - Fetal Alcohol Spectrum Disorders/epidemiology/*genetics/pathology
MH  - Fetus/pathology
MH  - Gastrulation/*drug effects
MH  - Gene Knockdown Techniques
MH  - Incidence
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nuclear Proteins/*genetics
MH  - Pregnancy
PMC - PMC6214710
MID - NIHMS986346
OTO - NOTNLM
OT  - Birth Defects
OT  - Development
OT  - Ethanol
OT  - Fetal Alcohol Syndrome
OT  - Transgenic Mice
EDAT- 2018/08/22 06:00
MHDA- 2019/11/07 06:00
PMCR- 2019/11/01
CRDT- 2018/08/22 06:00
PHST- 2018/07/06 00:00 [received]
PHST- 2018/08/16 00:00 [accepted]
PHST- 2018/08/22 06:00 [pubmed]
PHST- 2019/11/07 06:00 [medline]
PHST- 2018/08/22 06:00 [entrez]
PHST- 2019/11/01 00:00 [pmc-release]
AID - 10.1111/acer.13876 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2018 Nov;42(11):2136-2143. doi: 10.1111/acer.13876. Epub 
      2018 Sep 10.