Transcript Models in Genetics - Cherokee High School

Models in Genetics
Of Mice and Men
Patricia Sidelsky
BS/MS Biology
Cherokee High School
Marlton, NJ
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)
Genetic Models
 Bacteria - E. coli
 Yeast - Saccharomyces cerevisiae
 Plants - Corn - Zea mays and
Arabdopsis thaliana
 Worm - C. elegans
 Fruit fly - Drosophila melanogaster
Vertebrate Genetic Models
 Zebra fish - Brachydanio rerio
 Frog - Xenopus laevis
 Mouse - Mus musculus
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
Mouse Models and Diseases
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Epilepsy
Cystic fibrosis
Glaucoma
Heart Disease
Obesity
Parkinsons
Diabetes - Type I
Cancer
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
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)
Expression of Gene in
Mouse - Research on Sleeping
Disorders in Humans
 Narcolepsy
 Cataplexy
 Circadian rhythms
Mice and Science
 Mice have been bred by mouse fanciers since
the 1800’s
 Abbie Lathrop, a Massachusetts mouse
enthusiast began to breed mice in the early
1900’s for their interesting fur colors.
 Harvard University began to use them in
research
 This led indirectly to the development of
Jackson Laboratories in Maine
Fancy Mice
 Many varieties of
coat colors
determined by a
variety of genes
 The distribution and
color of pigments
Mouse Chromosomal analysis
Comparing a human and
mouse gene significant in
kidney disease
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
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
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.
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.
Transgenic Mice
Reporter genes
 Included and
expressed with the
gene of interest
 My be expressed at
the same
developmental
stage as well
Fluorescent Green Protein
Marker
Growth Hormone
 Promoter inserted
to increase the
production of
growth hormone
 Littermates
displaying normal
and transgene
Models for Human Disease
Obesity
 Growing concern in
obesity
 Studying genes that
effect weight
maintenance
and metabolism
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.
Knock Out Mice
Chimeric Mice
Chimeric Breeding
Thank you