# ETHANOL TERATOGENICITY AND SOD-1

> **NIH NIH R01** · MOUNT SINAI SCHOOL OF MEDICINE OF CUNY · 1994 · $157,154

## Abstract

Oxygen free radical damage has been implicated in nearly every aspect of
human development and disease.  The role of Cu/Zn superoxide dismutase
(SOD-1) an oxygen free radical scavenging enzyme, in preventing such
damage has been intensively studied.  Our laboratory has recently cloned
the genomic sequence for murine SOD-1, and identified a processed
pseudogene of this enzyme.  We will use the genomic clone to conduct
definitive experiments on the role of oxygen free radicals in abnormal
mouse development.  To attain this goal, we will perform insertional
disruption of the SOD-1 gene in mice by targeted mutagenesis in embryonic
stem (ES) cells, thereby to produce mice with either 50% of the normal
activity of SOD-1, no activity at all.  Such animals should have broad
applicability to studies of aging, environmental toxicology and
teratology.  In this proposal we focus our attention on teratology;
specifically, on the fetal alcohol syndrome (FAS).  FAS, a major
preventable cause of mental retardation in humans, can be mimicked in
mice, and oxygen free radicals have been implicated though not proven to
be mediators of ethanol (EtOH) teratogenicity.  Further, the role of
maternal versus fetal genotype in FAS susceptibility has not been clearly
separated.  By deleting the SOD-1 gene in an inbred mouse strain, we can
both test the role of oxygen free radicals in FAS, and at the same time
distinguish effects of maternal and fetal genotype on susceptibility.
Females carrying a deletion of SOD-1, when mated to normal males, will
gestate fetuses, half of which will be genetically wild type, and half
of which will be SOD-1 deletion carriers with 50% the normal level of
SOD-1 activity.  These fetuses can be studied for ethanol-induced
teratogenic effects and subsequently analyzed for their SOD-1 genotype.
Similarly, normal females mated to males heterozygous for the deletion
will provide a normal maternal environment to the genetically distinct
fetuses.  Finally, if mice homozygous for the SOD-1 deletion are viable,
these can be studied for increased sensitivity to EtOH using similar
mating and/or embryo transfer protocols.  We will also investigate
whether insertion of new SOD-1 genes by pronuclear microinjection can
confer resistance to EtOH teratogenicity.  These studies should provide
new insights into FAS, and establish a valuable new animal model for
mammalian teratology.  We also will study the evolution of this important
enzyme by sequencing and mapping the pseudogene.

## Key facts

- **NIH application ID:** 2198021
- **Project number:** 5R01HD020484-08
- **Recipient organization:** MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
- **Principal Investigator:** JON W GORDON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $157,154
- **Award type:** 5
- **Project period:** 1986-04-01 → 1997-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198021

## Citation

> US National Institutes of Health, RePORTER application 2198021, ETHANOL TERATOGENICITY AND SOD-1 (5R01HD020484-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198021. Licensed CC0.

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