Models in Genetics

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Models in Genetics

• Of Mice and Men
• Patricia Sidelsky
• BS/MS Biology
• Cherokee High School
• Marlton, NJ

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What is a Genetic Model ?

• Genes on chromosomes have been mapped
• Genome has been sequenced
• Significant for genetic content - relevance to
  man and society
• Homologous in function or expression to man(
  Mice)

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Genetic Models

• Bacteria - E. coli
• Yeast - Saccharomyces cerevisiae
• Plants - Corn - Zea mays and Arabdopsis thaliana
• Worm - C. elegans
• Fruit fly - Drosophila melanogaster

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Vertebrate Genetic Models

• Zebra fish - Brachydanio rerio
• Frog - Xenopus laevis
• Mouse - Mus musculus

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Why Mice?

• Vertebrate Model
• Mammal
• Used in Biochemical research - Cae and housing
  easily managed
• Short Generation time/ Breeding
• Size of litter
• Manipulation of embryos
• 96 homologous in genetic content to man
• 40,000 genes - similar in number to man

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Mouse Models and Diseases

• Epilepsy
• Cystic fibrosis
• Glaucoma
• Heart Disease
• Obesity
• Parkinsons
• Diabetes - Type I
• Cancer

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Mice and the Brain

• Recently a model of the mouse brain has been
  completed that may lead to possible cures for
  diseases such as Multiple sclerosis or even
  Mental Disorders such as autism or schizophrenia

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Early to Bed Gene

• Gene has been located in mouse brain that
  regulates wakefulness and sleep of the mouse
• Early to be gene
• Located in a portion of the brain called the SCN(
  superchiasmatic nucleus)

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Expression of Gene inMouse - Research on
Sleeping Disorders in Humans

• Narcolepsy
• Cataplexy
• Circadian rhythms

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Mice and Science

• Mice have been bred by mouse fanciers since the
  1800s
• Abbie Lathrop, a Massachusetts mouse enthusiast
  began to breed mice in the early 1900s for their
  interesting fur colors.
• Harvard University began to use them in research
• This led indirectly to the development of Jackson
  Laboratories in Maine

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Fancy Mice

• Many varieties of coat colors determined by a
  variety of genes
• The distribution and color of pigments

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Mouse Chromosomal analysis
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Comparing a human and mouse gene significant in
kidney disease
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Genetic manipulation of mouse DNA

• DNA is injected into early embryo
• Genes are implanted that enhance or silence gene
  expression
• New genes are incorporated into model organism
  genome

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Designer Genes

• 1. Make your DNA Using recombinant DNA methods,
  build molecules of DNA containing?the structural
  gene you wish to study
• Make sure that you include with the gene the
  correct promoter and expression controls that you
  need

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Gene Transfer

• Transform ES cells in culture
• Expose the cultured cells to the DNA so that some
  will incorporate it.
• Select for successfully transformed cells. Inject
  these cells into the inner cell mass (ICM) of
  mouse blastocysts.

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Transgenic Mice

• Pronucleus Method
• Transform fertilized eggs?Harvest freshly
  fertilized eggs before the sperm head has become
  a pronucleus.?Inject the male pronucleus with
  your DNA.
• When the pronuclei have fused to form the diploid
  zygote nucleus, allow the zygote to divide by
  mitosis to form a 2-cell embryo.

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Transgenic Mice
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Reporter genes

• Included and expressed with the gene of interest
• My be expressed at the same developmental stage
  as well

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Fluorescent Green Protein Marker
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Growth Hormone

• Promoter inserted to increase the production of
  growth hormone
• Littermates displaying normal and transgene

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Models for Human DiseaseObesity

• Growing concern in obesity
• Studying genes that effect weight maintenance
• and metabolism

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Knock Out Mice

• Gene is inactivated or nullified it is unable to
  be expressed
• Knockout mice are valuable tools for discovering
  the function(s) of genes for which mutant strains
  were not previously available.
• Knockout mice are often surprisingly unaffected
  by their deficiency. Many genes turn out not to
  be indispensable.

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Knock Out Mice
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Chimeric Mice
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Chimeric Breeding
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Thank you