Prenatal Alcohol Effects in Mice

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Prenatal Alcohol Effects in Mice
David Gilliam
Psychology Department University of Northern
Colorado
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Introduction

• Please view this PowerPoint presentation with the
  notes showing below each slide

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Facts about the fetal alcohol syndrome
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FAS is the 1 known cause of mental retardation
in the United States and one of the three leading
causes of birth defects.
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Each year over 40,000 American children are born
with defects because their mother drank alcohol
when pregnant.
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The effects of prenatal alcohol exposure never go
away. People with FAS have the disabilities they
are born with, including mental retardation,
throughout their lives.
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4. There is no known safe amount of alcohol for
a pregnant woman. When a woman drinks, her baby
drinks, because the alcohol passes directly
through the placenta to the baby.
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FAS Research with Mice

• Known Prenatal Development
• Genetic Differences to FAE
• Mapped Genome

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Genetic Strategies
1. Differences among Genetically Defined
Stocks 2. Maternal Effects Reciprocal
Cross 3. Cytoplasmic Influences Backcross
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Mice are useful because
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General Methods
C-Section FetalExamination
Drug Administration
Mating
I
or
0
9
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Day of Pregnancy
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Teratological MeasuresSpecific to Day 9 of
Gestation
1. Fetal Weight Deficits 2. Skeletal
Malformations - Forelimb - Rib/Vertebrae 3.
Soft Tissue Malformations - Kidney 4. Fetal
Mortality
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Finally, examination of internal organs often
reveals malformed kidneys as seen in the next
slide.
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Each type of malformation is thought to be under
different genetic control. As you might expect,
the frequency we see these malformations varies
among different mouse stocks.
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Genetic Strategies

• 1. Differences among Genetically Defined Stocks
• 2. Maternal Effects Reciprocal Cross
• 3. Cytoplasmic Influences Backcross

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Skeletal Malformations


NS
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Observed Prenatal Alcohol Effects in Mice
Inbred Strains
Selectively Bred









1


1
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Genetic Strategies
1. Differences among Genetically Defined
Stocks 2. Maternal Effects Reciprocal
Cross 3. Cytoplasmic Influences Backcross
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The answer to this question is important because
it will direct our attention toward studying
mechanisms that are under the influence of the
maternal genotype versus studying mechanisms that
are under the influence of the fetal genotype.
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Reciprocal Cross Mating Design
Male
H
L
HL
HH
H
Female
LL
LH
L
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Experimental expectations
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Experimental Results from Reciprocal
CrossMaternal Effect
HH
HL
Prenatal Alcohol Effect
Maternal Effect
LH
LL
LL
HH
HL/LH
Fetal Genotype
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Observed Maternal Effects
Reciprocal Cross



Not Measured

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Reasons for a Maternal Effect
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Reasons for a Maternal Effect
1. Genes are carried on the sex chromosomes
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Reasons for a Maternal Effect
2. Maternal uterine environments are different
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Reasons for a Maternal Effect
3. Genomic imprinting
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Reasons for a Maternal Effect
4. Factors are transmitted through the egg
cytoplasm
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Genetic Strategies
1. Differences among Genetically Defined
Stocks 2. Maternal Effects Reciprocal
Cross 3. Cytoplasmic Influences Backcross
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Reciprocal Cross Mating Design
Male
H
L
HL
HH
H
Female
LL
LH
L
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Backcross Mating Design
Male
HL
HL.H
Female
LH.H
LH
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No Cytoplasmic Effect
Maternal Effect on Skeletal Malformations
75
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B6B6
Skeletal Malformations ()
B6D2
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Maternal Effect
D2B6
D2D2
0
B6D2.B6
D2B6.B6
B6B6
B6D2/D2B6
D2D2
Fetal Genotype
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No Cytoplasmic Effect
Maternal Effect on Skeletal Malformations
75
50
B6B6
Skeletal Malformations ()
B6D2
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Maternal Effect
D2B6
D2D2
0
B6D2.B6
D2B6.B6
B6B6
B6D2/D2B6
D2D2
Fetal Genotype
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Conclusions
1. Genetic Differences to Prenatal Alcohol
Effects 2. Maternal Genetic Influences on
Specific Measures 3. Sex-linked Genes and
Cytoplasmicly-transmitted Factors are Not
Responsible 4. Uterine Environment or Genomic
Imprinting
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Future Directions
1. Extent of Genetic Variation 2. Apply Genetic
Techniques to Answer Questions 3. Apply
Knowledge to Human Genome
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Embryo Transfer
B6 Female
D2 Female
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Thank You