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