How Did the Chicken Cross the TestSmart Road

1
How Did the Chicken Cross the TestSmart Road?

• Susan Smith, Ph.D.
• Molecular Environmental Toxicology
• University of Wisconsin-Madison

2
Three Reasons to Use a Chick Embryo Model for DNT

• Low cost, potential for high throughput
• Neurodevelopment is well-studied
• Popular model for neurobehavioral assessments

3
Chick Embryos are Cheep

• Low animal costs
• Low maintenance
• High-throughput incubation hatch
• Tanks or special rooms not needed
• High embryo volume available
• Vendors supply 105 fertile eggs weekly

4
Handling Can Be Automated
High-throughput treats 20,000 to 60,000
eggs per hour. Automated injection, egg
decapitation, fluid collection.
5
Uniformity of Eggs Embryos

• SPF embryos readily available
• Consistent egg size, composition
• Uniform chemical exposure
• Standardized genetic lines
• Precise control of developmental stage exposure
  timing
• Accommodate both hydrophobic hydrophilic
  chemicals

6
Chick Development is Rapid
7
Ideal for DNT Screens

• Classic model of CNS development
• neurogenesis, migration, outgrowth,
  synaptogenesis, gliogenesis, apoptosis
• Neuroanatomy is well-characterized
• Plethora of analytical reagents
• Explants primary lines already used in
  toxicology screens
• Monitoring manipulation is non-invasive

8
Genetic Accessibility

• Closest non-mammalian
• vertebrate model
• Developmentally conserved
• molecular, cellular, mechanistic
• Genome published in 2004
• Strong synteny with human
• Affymatrix arrays available
• Genetic manipulation is feasible
• Germline reporter strains underway
• Amenable to multi-generation studies
• Sexual maturity chicken 18 wks, quail 8 wks

9
Long-Standing Model for Behavioral Testing

• Extensive array of neurobehavioral tests
• Motor Sensory
• Learning Memory
• Integrate behavior w/ genes, anatomy,
  endocrinology
• Established cognates w/ human mammals

10
Chick Embryo is Predictive of Human Toxicants

• Good correlation with mammalian and human
  dose-responses
• Directly tests the conceptus
• Pharmacokinetics are straight-forward
• Birds are proven monitors of environ-mental
  toxins endocrine disruptors

11
Some Teratogens Studied in Chick

• Accutane
• Aflatoxin B1
• Coumarin
• DDT
• Dopamine excess
• Estrogens
• Ethanol
• Folate deficiency
• Lead

• MeHg
• Organophosphates
• PCBs
• Retinoid deficiency
• Selenium
• TCDD / dioxin
• Thalidomide
• Trichloroethylene

12
Chick Embryo as Tier 1 Screen

• Well studied neurodevelopment
• Well studied neurobehavior
• Off the shelf automated handling
• Low expense
• Highest non-mammalian embryo model
• Evolutionary Conserved