Models in GeneticsModels in Genetics
Of Mice and Men
Patricia SidelskyBS/MS Biology
Cherokee High SchoolMarlton, NJ
Of Mice and Men
Patricia SidelskyBS/MS Biology
Cherokee High SchoolMarlton, NJ
What is a Genetic Model ?What is a Genetic Model ?
Genes on chromosomes have been mapped
Genome has been sequencedSignificant for genetic content -
relevance to man and society Homologous in function or
expression to man( Mice)
Genes on chromosomes have been mapped
Genome has been sequencedSignificant for genetic content -
relevance to man and society Homologous in function or
expression to man( Mice)
Genetic ModelsGenetic Models
Bacteria - E. coliYeast - Saccharomyces cerevisiaePlants - Corn - Zea mays and
Arabdopsis thalianaWorm - C. elegansFruit fly - Drosophila melanogaster
Bacteria - E. coliYeast - Saccharomyces cerevisiaePlants - Corn - Zea mays and
Arabdopsis thalianaWorm - C. elegansFruit fly - Drosophila melanogaster
Vertebrate Genetic ModelsVertebrate Genetic Models
Zebra fish - Brachydanio rerioFrog - Xenopus laevisMouse - Mus musculus
Zebra fish - Brachydanio rerioFrog - Xenopus laevisMouse - Mus musculus
Why Mice?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
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
Mouse Models and Diseases
Epilepsy Cystic fibrosis Glaucoma Heart Disease Obesity Parkinsons Diabetes - Type I Cancer
Epilepsy Cystic fibrosis Glaucoma Heart Disease Obesity Parkinsons Diabetes - Type I Cancer
Mice and the BrainMice 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
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 GeneEarly to Bed Gene
Gene has been located in mouse brain that regulates wakefulness and sleep of the mouse
Early to be geneLocated in a portion of the brain
called the SCN( superchiasmatic nucleus)
Gene has been located in mouse brain that regulates wakefulness and sleep of the mouse
Early to be geneLocated in a portion of the brain
called the SCN( superchiasmatic nucleus)
Expression of Gene inMouse - Research on Sleeping Disorders in
Humans
Expression of Gene inMouse - Research on Sleeping Disorders in
Humans Narcolepsy Cataplexy Circadian rhythms
Narcolepsy Cataplexy Circadian rhythms
Mice and ScienceMice 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
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 MiceFancy Mice
Many varieties of coat colors determined by a variety of genes
The distribution and color of pigments
Many varieties of coat colors determined by a variety of genes
The distribution and color of pigments
Mouse Chromosomal analysis
Mouse Chromosomal analysis
Comparing a human and mouse gene significant in
kidney disease
Comparing a human and mouse gene significant in
kidney disease
Genetic manipulation of mouse DNA
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
DNA is injected into early embryo
Genes are implanted that enhance or silence gene expression
New genes are incorporated into model organism genome
Designer GenesDesigner 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
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 TransferGene Transfer
Transform ES cells in cultureExpose 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.
Transform ES cells in cultureExpose 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 MiceTransgenic 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.
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 MiceTransgenic Mice
Reporter genes Reporter genes
Included and expressed with the gene of interest
My be expressed at the same developmental stage as well
Included and expressed with the gene of interest
My be expressed at the same developmental stage as well
Fluorescent Green Protein Marker
Fluorescent Green Protein Marker
Growth HormoneGrowth Hormone
Promoter inserted to increase the production of growth hormone
Littermates displaying normal and transgene
Promoter inserted to increase the production of growth hormone
Littermates displaying normal and transgene
Models for Human DiseaseObesity
Models for Human DiseaseObesity
Growing concern in obesity
Studying genes that effect weight maintenance
and metabolism
Growing concern in obesity
Studying genes that effect weight maintenance
and metabolism
Knock Out MiceKnock 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.
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 MiceKnock Out Mice
Chimeric MiceChimeric Mice
Chimeric BreedingChimeric Breeding
Thank youThank you
