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Models in Genetics Of Mice and Men Patricia Sidelsky BS/MS Biology Cherokee High School Marlton, NJ Of Mice and Men Patricia Sidelsky BS/MS Biology Cherokee.

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Presentation on theme: "Models in Genetics Of Mice and Men Patricia Sidelsky BS/MS Biology Cherokee High School Marlton, NJ Of Mice and Men Patricia Sidelsky BS/MS Biology Cherokee."— Presentation transcript:

1 Models in Genetics Of Mice and Men Patricia Sidelsky BS/MS Biology Cherokee High School Marlton, NJ Of Mice and Men Patricia Sidelsky BS/MS Biology Cherokee High School Marlton, NJ

2 What is a Genetic Model ? G Genes on chromosomes have been mapped G Genome has been sequenced G Significant for genetic content - relevance to man and society G Homologous in function or expression to man( Mice) G Genes on chromosomes have been mapped G Genome has been sequenced G Significant for genetic content - relevance to man and society G Homologous in function or expression to man( Mice)

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

4 Vertebrate Genetic Models G Zebra fish - Brachydanio rerio G Frog - Xenopus laevis G Mouse - Mus musculus G Zebra fish - Brachydanio rerio G Frog - Xenopus laevis G Mouse - Mus musculus

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

6 Mouse Models and Diseases G Epilepsy G Cystic fibrosis G Glaucoma G Heart Disease G Obesity G Parkinsons G Diabetes - Type I G Cancer G Epilepsy G Cystic fibrosis G Glaucoma G Heart Disease G Obesity G Parkinsons G Diabetes - Type I G Cancer

7 Mice and the Brain G 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

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

9 Expression of Gene in Mouse - Research on Sleeping Disorders in Humans G Narcolepsy G Cataplexy G Circadian rhythms

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

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12 Fancy Mice G Many varieties of coat colors determined by a variety of genes G The distribution and color of pigments

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18 Mouse Chromosomal analysis

19 Comparing a human and mouse gene significant in kidney disease

20 Genetic manipulation of mouse DNA G DNA is injected into early embryo G Genes are implanted that enhance or silence gene expression G New genes are incorporated into model organism genome G DNA is injected into early embryo G Genes are implanted that enhance or silence gene expression G New genes are incorporated into model organism genome

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

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

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

24 Transgenic Mice

25 Reporter genes G Included and expressed with the gene of interest G My be expressed at the same developmental stage as well G Included and expressed with the gene of interest G My be expressed at the same developmental stage as well

26 Fluorescent Green Protein Marker

27 Growth Hormone G Promoter inserted to increase the production of growth hormone G Littermates displaying normal and transgene G Promoter inserted to increase the production of growth hormone G Littermates displaying normal and transgene

28 Models for Human Disease Obesity G Growing concern in obesity G Studying genes that effect weight maintenance and metabolism G Growing concern in obesity G Studying genes that effect weight maintenance and metabolism

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

30 Knock Out Mice

31 Chimeric Mice

32 Chimeric Breeding

33 Thank you


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